Satomi Tomida, Teruhide Koyama, Etsuko Ozaki, Naoyuki Takashima, Midori Morita, Koichi Sakaguchi, Yasuto Naoi, Yuichiro Nishida, Megumi Hara, Asahi Hishida, Takashi Tamura, Rieko Okada, Yoko Kubo, Jun Otonari, Hiroaki Ikezaki, Yohko Nakamura, Miho Kusakabe, Shiroh Tanoue, Chihaya Koriyama, N Yuriko Koyanagi, Hidemi Ito, Sadao Suzuki, Takahiro Otani, Naoko Miyagawa, Yukiko Okami, Kokichi Arisawa, Takeshi Watanabe, Kiyonori Kuriki, Kenji Wakai and Keitaro Matsuo : Seven-plus hours of daily sedentary time and the subsequent risk of breast cancer: Japan Multi-Institutional Collaborative Cohort Study., Cancer Science, Vol.115, No.2, 611-622, 2024.
(要約)
This study aimed to investigate the association between daily sedentary time and the risk of breast cancer (BC) in a large Japanese population. The participants were 36,023 women aged 35-69years from the Japan Multi-Institutional Collaborative Cohort Study. Cox proportional hazards analysis was used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for BC incidence in relation to time spent sedentarily (categorical variables: <7 and 7hours/day [h/d]). Additionally, the associations of BC incidence to the joint effect of sedentary time with each component of physical activity, such as leisure-time metabolic equivalents (METs), frequency of leisure-time physical activity, and daily walking time, were examined. During 315,189 person-years of follow-up, 554 incident cases of BC were identified. When compared to participants who spent <7h/d sedentary, those who spent 7h/d sedentary have a significantly higher risk of BC (HR, 1.36; 95% CI, 1.07-1.71). The corresponding HRs among participants who spent 7h/d sedentary with more physical activity, such as 1h/d for leisure-time METs, 3days/week of leisure-time physical activity, and 1h/d of daily walking were 1.58 (95% CI, 1.11-2.25), 1.77 (95% CI, 1.20-2.61), and 1.42 (95% CI, 1.10-1.83), respectively, compared with those who spent <7h/d sedentary. This study found that spending 7h/d of sedentary time is associated with the risk of BC. Neither leisure-time physical activity nor walking had a BC-preventive effect in those with 7h/d of sedentary time.
Daisaku Nishimoto, Rie Ibusuki, Ippei Shimoshikiryo, Kenichi Shibuya, Shiroh Tanoue, Chihaya Koriyama, Toshiro Takezaki, Isao Oze, Hidemi Ito, Asahi Hishida, Takashi Tamura, Yasufumi Kato, Yudai Tamada, Yuichiro Nishida, Chisato Shimanoe, Sadao Suzuki, Takeshi Nishiyama, Etsuko Ozaki, Satomi Tomida, Kiyonori Kuriki, Naoko Miyagawa, Keiko Kondo, Kokichi Arisawa, Takeshi Watanabe, Hiroaki Ikezaki, Jun Otonari, Kenji Wakai and Keitaro Matsuo : Association between awareness of limiting food intake and all-cause mortality: A cohort study in Japan, Journal of Epidemiology, 2023.
(要約)
Improving diets requires an awareness of the need to limit foods for which excessive consumption is a health problem. Since there are limited reports on the link between this awareness and mortality risk, we examined the association between awareness of limiting food intake (energy, fat, and sweets) and all-cause mortality in a Japanese cohort study. Participants comprised 58,772 residents (27,294 men; 31,478 women) aged 35-69 years who completed baseline surveys of the Japan Multi-Institutional Collaborative Cohort Study from 2004 to 2014. Hazard ratios (HRs) for all-cause mortality and 95% confidence intervals (CIs) were estimated by sex using a Cox proportional hazard model, with adjustment for related factors. Mediation analysis with fat intake as a mediator was also conducted. The mean follow-up period was 11 years and 2,516 people died. Estimated energy and fat intakes according to the Food Frequency Questionnaire were lower in those with awareness of limiting food intake than in those without this awareness. Women with awareness of limiting fat intake showed a significant decrease in mortality risk (HR=0.73; 95% CI, 0.55 to 0.94). Mediation analysis revealed that this association was due to the direct effect of the awareness of limiting fat intake and that the total effect was not mediated by actual fat intake. Awareness of limiting energy or sweets intake was not related to mortality risk reduction. Awareness of limiting food intake had a limited effect on reducing all-cause mortality risk.
(キーワード)
awareness of limiting food intake / all-cause mortality / cohort study
Naoko Matsui, Keiko Tanaka, Mitsuyo Ishida, Yohei Yamamoto, Yuri Matsubara, Reiko Saika, Takahiro Iizuka, Koshi Nakamura, Nagato Kuriyama, Makoto Matsui, Kokichi Arisawa, Yosikazu Nakamura, Ryuji Kaji, Satoshi Kuwabara and Yuishin Izumi : Prevalence, Clinical Profiles, and Prognosis of Stiff-Person Syndrome in a Japanese Nationwide Survey., Neurology® Neuroimmunology & Neuroinflammation, Vol.10, No.6, e200165, 2023.
(要約)
This study provides the current epidemiologic and clinical status of SPS in Japan. The symptom onset to the diagnosis of SPS was longer in patients with high-titer GAD65 antibodies than in those with low-titer GAD65 antibodies. The outcome of patients with SPS was generally favorable, but more aggressive immunotherapies are necessary for GAD65-positive patients with SPS.
(キーワード)
Adult / Aged / Aged, 80 and over / Female / Humans / Male / Middle Aged / Antibodies / East Asian People / Glutamate Decarboxylase / Immunotherapy / Prevalence / Prognosis / Stiff-Person Syndrome
Mineko Tsukamoto, Asahi Hishida, Takashi Tamura, Mako Nagayoshi, Rieko Okada, Yoko Kubo, Yasufumi Kato, Nobuyuki Hamajima, Yuichiro Nishida, Chisato Shimanoe, Rie Ibusuki, Kenichi Shibuya, Naoyuki Takashima, Yasuyuki Nakamura, Miho Kusakabe, Yohko Nakamura, N Yuriko Koyanagi, Isao Oze, Takeshi Nishiyama, Sadao Suzuki, Isao Watanabe, Daisuke Matsui, Jun Otonari, Hiroaki Ikezaki, Sakurako Katsuura-Kamano, Kokichi Arisawa, Kiyonori Kuriki, Masahiro Nakatochi, Yukihide Momozawa, Kenji Takeuchi, Kenji Wakai and Keitaro Matsuo : GWAS of folate metabolism with gene-environment interaction analysis revealed the possible role of lifestyles in the control of blood folate metabolites in Japanese - the J-MICC Study., Journal of Epidemiology, Vol.34, No.5, 228-237, 2023.
(要約)
The present genome-wide association study (GWAS) aimed to reveal the genetic loci associated with folate metabolites, as well as to detect related gene-environment interactions in Japanese. We conducted the GWAS of plasma homocysteine (Hcy), folic acid (FA), and vitamin B (VB) levels in the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study participants who joined from 2005 to 2012, and also estimated gene-environment interactions. In the replication phase, we used data from the Yakumo Study conducted in 2009. In the discovery phase, data of 2,263 participants from four independent study sites of the J-MICC Study were analyzed. In the replication phase, data of 573 participants from the Yakumo Study were analyzed. For Hcy, MTHFR locus on chr 1, NOX4 on chr 11, CHMP1A on chr 16, and DPEP1 on chr 16 reached genome-wide significance (P < 5 × 10). MTHFR also associated with FA, and FUT2 on chr 19 associated with VB. We investigated gene-environment interactions in both studies and found significant interactions between MTHFR C677T and ever drinking, current drinking, and physical activity >33% on Hcy (β = 0.039, 0.038 and -0.054, P = 0.018, 0.021 and <0.001, respectively) and the interaction of MTHFR C677T with ever drinking on FA (β = 0.033, P = 0.048). The present GWAS revealed the folate metabolism-associated genetic loci and gene-environment interactions with drinking and physical activity in Japanese, suggesting the possibility of future personalized cardiovascular disease prevention.
(キーワード)
Humans / Folic Acid / Japan / Genome-Wide Association Study / Gene-Environment Interaction / Male / Female / Middle Aged / Homocysteine / Life Style / Adult / Aged / Methylenetetrahydrofolate Reductase (NADPH2) / Vitamin B 12 / Cohort Studies / Polymorphism, Single Nucleotide / East Asian People
Takeshi Watanabe, Kokichi Arisawa, Tien Van Nguyen, Masashi Ishizu, Sakurako Katsuura-Kamano, Asahi Hishida, Takashi Tamura, Yasufumi Kato, Rieko Okada, Rie Ibusuki, Chihaya Koriyama, Sadao Suzuki, Takahiro Otani, Teruhide Koyama, Satomi Tomida, Kiyonori Kuriki, Naoyuki Takashima, Naoko Miyagawa, Kenji Wakai and Keitaro Matsuo : Coffee and Metabolic Phenotypes: A Cross-sectional Analysis of the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study, Nutrition, Metabolism, and Cardiovascular Diseases : NMCD, Vol.33, No.3, 620-630, 2023.
(要約)
To date, the relationship between coffee consumption and metabolic phenotypes has hardly been investigated and remains controversial. Therefore, the aim of this cross-sectional study is to examine the associations between coffee consumption and metabolic phenotypes in a Japanese population. We analyzed the data of 26,363 subjects (aged 35-69 years) in the baseline survey of the Japan Multi-Institutional Collaborative Cohort Study. Coffee consumption was assessed using a questionnaire. Metabolic Syndrome (MetS) was defined according to the Joint Interim Statement Criteria of 2009, using body mass index (BMI) instead of waist circumference. Subjects stratified by the presence or absence of obesity (normal weight: BMI <25 kg/m; obesity: BMI ≥25 kg/m) were classified by the number of MetS components (metabolically healthy: no components; metabolically unhealthy: one or more components) other than BMI. In multiple logistic regression analyses adjusted for sex, age, and other potential confounders, high coffee consumption (≥3 cups/day) was associated with a lower prevalence of MetS and metabolically unhealthy phenotypes both in normal weight (OR 0.83, 95% CI 0.76-0.90) and obese subjects (OR 0.83, 95% CI 0.69-0.99). Filtered/instant coffee consumption was inversely associated with the prevalence of MetS and metabolically unhealthy phenotypes, whereas canned/bottled/packed coffee consumption was not. The present results suggest that high coffee consumption, particularly filtered/instant coffee, is inversely associated with the prevalence of metabolically unhealthy phenotypes in both normal weight and obese Japanese adults.
(キーワード)
Humans / Cross-Sectional Studies / Coffee / Cohort Studies / Japan / Metabolic Syndrome / Obesity / Body Mass Index / Phenotype / Risk Factors
Kaori Kitaoka, Katsuyuki Miura, Naoyuki Takashima, Aya Kadota, Akiko Harada, Yasuyuki Nakamura, Yoshikuni Kita, Yuichiro Yano, Takashi Tamura, Mako Nagayoshi, Rieko Okada, Yoko Kubo, Sadao Suzuki, Takeshi Nishiyama, Shiroh Tanoue, Chihaya Koriyama, Kiyonori Kuriki, Kokichi Arisawa, Sakurako Katsuura-Kamano, Yuichiro Nishida, Chisato Shimanoe, Etsuko Ozaki, Daisuke Matsui, Hiroaki Ikezaki, Jun Otonari, Isao Oze, Yuriko N. Koyanagi, Yohko Nakamura, Miho Kusakabe, Kenji Wakai and Keitaro Matsuo : Association between dietary patterns and serum low density lipoprotein cholesterol in Japanese women and men: The Japan Multi-Institutional Collaborative Cohort (J-MICC) Study, Journal of Atherosclerosis and Thrombosis, 2023.
(要約)
The association between dietary patterns and serum low density lipoprotein (LDL) cholesterol would be changing in recent dietary habits in Japan. We investigated the relationship between dietary patterns and serum LDL cholesterol in a large general population. From the baseline survey of Japan Multi-Institutional Collaborative Cohort Study between 2005 and 2013, 27,237 participants (13,994 were women) aged 35-69 years were cross-sectionally analyzed. Using a semi-quantitative food frequency questionnaire, five major sex-specific dietary patterns were identified using factor analysis. We assessed serum LDL cholesterol by quintiles of dietary pattern factor score. We identified dietary patterns; "vegetable rich pattern" , "meat and fried food rich pattern" and "high bread and low rice pattern" in women and men; "fish and shellfish rich pattern" and "high confectioneries and low alcohol pattern" in men; "healthy Japanese diet pattern" and "high alcohol and low rice pattern" in women. Serum LDL cholesterol in men was associated with "high bread and low rice pattern" score (Q5 was 4.2 mg/dL higher than Q1, p for trend <0.001) and "high confectioneries and low alcohol pattern" scores (Q5 was 9.5 mg/dL higher than Q1, p for trend <0.001). In women, serum LDL cholesterol was associated with "high bread and low rice pattern" score (Q5 was 7.1 mg/dL higher than Q1, p for trend <0.001). Some recent dietary patterns in Japan were associated with serum LDL cholesterol. Serum LDL cholesterol was associated with high bread and low rice pattern in both sex, and high confectioneries and low alcohol pattern in men.
Sho Nakamura, Xuemin Fang, Yoshinobu Saito, Hiroto Narimatsu, Azusa Ota, Hiroaki Ikezaki, Chisato Shimanoe, Keitaro Tanaka, Yoko Kubo, Mineko Tsukamoto, Takashi Tamura, Asahi Hishida, Isao Oze, Yuriko N. Koyanagi, Yohko Nakamura, Miho Kusakabe, Toshiro Takezaki, Daisaku Nishimoto, Sadao Suzuki, Takahiro Otani, Nagato Kuriyama, Daisuke Matsui, Kiyonori Kuriki, Aya Kadota, Yasuyuki Nakamura, Kokichi Arisawa, Sakurako Katsuura-Kamano, Masahiro Nakatochi, Yukihide Momozawa, Michiaki Kubo, Kenji Takeuchi and Kenji Wakai : Effects of gene-lifestyle interactions on obesity based on a multi-locus risk score: a cross-sectional analysis, PLoS ONE, Vol.18, No.2, e0279169, 2023.
(要約)
The relationship between lifestyle and obesity is a major focus of research. Personalized nutrition, which utilizes evidence from nutrigenomics, such as gene-environment interactions, has been attracting attention in recent years. However, evidence for gene-environment interactions that can inform treatment strategies is lacking, despite some reported interactions involving dietary intake or physical activity. Utilizing gene-lifestyle interactions in practice could aid in optimizing interventions according to genetic risk. This study aimed to elucidate the effects of gene-lifestyle interactions on body mass index (BMI). Cross-sectional data from the Japan Multi-Institutional Collaborative Cohort Study were used. Interactions between a multi-locus genetic risk score (GRS), calculated from 76 ancestry-specific single nucleotide polymorphisms, and nutritional intake or physical activity were assessed using a linear mixed-effect model. The mean (standard deviation) BMI and GRS for all participants (n = 12,918) were 22.9 (3.0) kg/m2 and -0.07 (0.16), respectively. The correlation between GRS and BMI was r(12,916) = 0.13 (95% confidence interval [CI] 0.11-0.15, P < 0.001). An interaction between GRS and saturated fatty acid intake was observed (β = -0.11, 95% CI -0.21 to -0.02). An interaction between GRS and n-3 polyunsaturated fatty acids was also observed in the females with normal-weight subgroup (β = -0.12, 95% CI -0.22 to -0.03). Our results provide evidence of an interaction effect between GRS and nutritional intake and physical activity. This gene-lifestyle interaction provides a basis for developing prevention or treatment interventions for obesity according to individual genetic predisposition.
(キーワード)
Female / Humans / Cross-Sectional Studies / Cohort Studies / Obesity / Risk Factors / Genetic Predisposition to Disease / Life Style / Polymorphism, Single Nucleotide / Body Mass Index
Although many observational studies have demonstrated significant relationships between obesity and cardiometabolic traits, the causality of these relationships in East Asians remains to be elucidated. We conducted individual-level Mendelian randomization (MR) analyses targeting 14,083 participants in the Japan Multi-Institutional Collaborative Cohort Study, and two-sample MR analyses using summary statistics based on genome-wide association study data from 173,430 Japanese. Using 83 body mass index-related loci, genetic risk scores (GRS) for BMI were calculated, and the effects of BMI on cardiometabolic traits were examined for individual-level MR analyses by the two-stage least squares estimator method. The β-coefficients and standard errors for the per-allele association of each single-nucleotide polymorphism as well as all outcomes, or odds ratios with 95% confidence intervals were calculated in the two-sample MR analyses. In individual-level MR analyses, the GRS of BMI was not significantly associated with any cardiometabolic traits. In two-sample MR analyses, higher BMI was associated with higher risks of higher blood pressure, triglycerides, uric acid, lower high-density-lipoprotein cholesterol and eGFR. The associations of BMI with type 2 diabetes in two-sample MR analyses were inconsistent by different methods, including the directions. The results of this study suggest that, even among the Japanese, an East Asian population with low levels of obesity, higher BMI could be causally associated with the development of a variety of cardiometabolic traits. Causality in those associations should be clarified in future studies with larger populations, especially those of BMI with type 2 diabetes.
During the follow-up (mean, 8.4 ± 2.5 years), 1,492 mortalities were recorded, and the prevalence of taking hypnotics was 4.2%. Hypnotic use was associated with significantly greater risk of all-cause mortality, even after adjustment for the covariates (HR, 1.32; 95% CI, 1.07-1.63). The association between hypnotic use and all-cause mortality was robust in males (HR, 1.51; 95% CI, 1.15-1.96), and participants aged <60 years (HR, 1.75; 95% CI, 1.21-2.54).
Akiko Hanyuda, Atsushi Goto, Masahiro Nakatochi, Yoichi Sutoh, Akira Narita, Shiori Nakano, Ryoko Katagiri, Kenji Wakai, Naoyuki Takashima, Teruhide Koyama, Kokichi Arisawa, Issei Imoto, Yukihide Momozawa, Kozo Tanno, Atsushi Shimizu, Atsushi Hozawa, Kengo Kinoshita, Taiki Yamaji, Norie Sawada, Masao Iwagami, Kenya Yuki, Kazuo Tsubota, Kazuno Negishi, Keitaro Matsuo, Masayuki Yamamoto, Makoto Sasaki, Shoichiro Tsugane and Motoki Iwasaki : Association Between Glycemic Traits and Primary Open-Angle Glaucoma: A Mendelian Randomization Study in the Japanese Population, American Journal of Ophthalmology, Vol.245, 193-201, 2022.
(要約)
A meta-analysis suggests a relationship between abnormal glucose metabolism and primary open-angle glaucoma (POAG); however, the causal association between them remains controversial. We therefore conducted a Mendelian randomization (MR) study to assess the causal association between genetically predicted glycemic traits and the risk of POAG. Two-sample MR design. We examined the genetically predicted measures of fasting glucose, hemoglobin A1c (HbA1c), and fasting C-peptide, in relation to POAG. For the single nucleotide polymorphism (SNP)-exposure analyses, we meta-analyzed the study-level genome-wide associations of fasting glucose levels (n = 17,289; n of SNPs = 34), HbA1c (n = 52,802; n of SNPs = 43), and fasting C-peptide levels (n=1666; n of SNPs = 17) from the Japanese Consortium of Genetic Epidemiology studies. We used summary statistics from the BioBank Japan projects (n = 3980 POAG cases and 18,815 controls) for the SNP-outcome association. We observed no association of genetically predicted HbA1c and fasting C-peptide with POAG. The MR inverse-variance-weighted (IVW) odds ratios (ORs) were 1.44 (95% confidence interval [CI], 0.78-2.65; P = .25) for HbA1c (per 1% increment) and 0.92 (95% CI, 0.56-1.53; P = .76) for fasting C-peptide (per 2-fold increment). A significant association between fasting glucose (per 10 mg/dL-increment) and POAG was observed according to the MR IVW analysis (OR = 1.48 [95% CI, 1.10-1.79, P = .009]); however, sensitivity analyses, including MR-Egger and weighted-median methods, did not support this association (P > .10). We did not observe strong evidence to support the association between genetically predicted glycemic traits and POAG in the Japanese population.
(キーワード)
Humans / Mendelian Randomization Analysis / Glycated Hemoglobin / Genome-Wide Association Study / C-Peptide / East Asian People / Glaucoma, Open-Angle / Risk Factors / Polymorphism, Single Nucleotide / Glucose
Previous studies using objective parameters have shown that irregular sleep is associated with the disease incidence, progression, or mortality. This study aimed to determine the association between subjective sleep duration and sleep regularity, with mortality in a large population. Participants were from the Japan Multi-Institutional Collaborative Cohort study. We obtained information from each participant on sleep duration, sleep regularity, and demographics and overall lifestyle using self-administered questionnaires. We defined sleep regularity according to participants' subjective assessment of sleep/wake time regularity. Participants (n = 81,382, mean age: 58.1 ± 9.1years, males: 44.2%) were classified into 6 groups according to sleep duration and sleep regularity. Hazard ratios (HR) for time-to-event of death were calculated using the Cox proportional hazards model. The mean follow-up period was 9.1 years and the mean sleep duration was 6.6 h/day. Irregular sleep significantly increased the risk of all-cause mortality in all models compared with regular sleep (HR 1.30, 95% confidence interval; CI, 1.18-1.44), regardless of sleep duration. Multivariable analysis of the 6 groups by sleep pattern (sleep regularity and duration) showed irregular sleep and sleep durations of <6 h/day, 6 to <8 h/day, or 8 h/day were associated with a 1.2-1.5-fold increases in mortality, compared to regular sleep and sleep duration of 6 to <8 h/day. Our study shows an association between sleep irregularity and all-cause mortality in a large Japanese population. Our findings provide further confirmation of the need to consider not only sleep duration, but also the regularity aspect of sleep schedules.
Genetic factors play a role in individual differences in pain experience. Here, we performed a genome-wide association study (GWAS) to identify novel loci regulating pain processing. We conducted a 2-stage GWAS and the candidate single-nucleotide polymorphisms (SNPs) association study on pain experience using an exploratory cohort of patients with cancer pain. The confirmatory cohort comprised of participants from the general population with and without habitual use of analgesic medication. In the exploratory cohort, we evaluated pain intensity using a numerical rating scale, recorded daily opioid dosages, and calculated pain reduction rate. In the confirmatory cohort, pain experience was defined as habitual nonsteroidal anti-inflammatory drug usage. Using linear regression models, we identified candidate SNP in the exploratory samples, and tested the association between phenotype and experienced pain in the confirmatory samples. We found 1 novel SNP (rs11764598)-located on the gene encoding for pleiotrophin on chromosome 7-that passed the genome-wide suggestive significance at 20% false discovery rate (FDR) correction in the exploratory samples of patients with cancer pain (P = 1.31 × 10-7, FDR = 0.101). We confirmed its significant association with daily analgesic usage in the confirmatory cohort (P = .028), although the minor allele affected pain experience in an opposite manner. We identified a novel genetic variant associated with pain experience. Further studies are required to validate the role of pleiotrophin in pain processing.
(キーワード)
Adult / Analgesics / Analgesics, Opioid / Anti-Inflammatory Agents / Cancer Pain / Carrier Proteins / Case-Control Studies / Cytokines / Genome-Wide Association Study / Humans / Japan / Nucleotides / Polymorphism, Single Nucleotide
Tien Van Nguyen, Kokichi Arisawa, Sakurako Katsuura-Kamano, Masashi Ishizu, Mako Nagayoshi, Rieko Okada, Asahi Hishida, Takashi Tamura, Megumi Hara, Keitaro Tanaka, Daisaku Nishimoto, Keiichi Shibuya, Teruhide Koyama, Isao Watanabe, Sadao Suzuki, Takeshi Nishiyama, Kiyonori Kuriki, Yasuyuki Nakamura, Yoshino Saito, Hiroaki Ikezaki, Jun Otonari, Yuriko N. Koyanagi, Keitaro Matsuo, Haruo Mikami, Miho Kusakabe, Kenji Takeuchi and Kenji Wakai : Associations of metabolic syndrome and metabolically unhealthy obesity with cancer mortality: The Japan Multi-Institutional Collaborative Cohort (J-MICC) Study, PLoS ONE, Vol.17, No.7, e0269550, 2022.
(要約)
The association between metabolic syndrome (MetS) and the risk of death from cancer is still a controversial issue. The purpose of this study was to examine the associations of MetS and metabolically unhealthy obesity (MUHO) with cancer mortality in a Japanese population. We used data from the Japan Multi-Institutional Collaborative Cohort Study. The study population consisted of 28,554 eligible subjects (14,103 men and 14,451 women) aged 35-69 years. MetS was diagnosed based on the criteria of the National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III) and the Japan Society for the Study of Obesity (JASSO), using the body mass index instead of waist circumference. The Cox proportional hazards analysis was used to estimate adjusted hazard ratios (HR) and 95% confidence intervals (CI) for total cancer mortality in relation to MetS and its components. Additionally, the associations of obesity and the metabolic health status with cancer mortality were examined. During an average 6.9-year follow-up, there were 192 deaths from cancer. The presence of MetS was significantly correlated with increased total cancer mortality when the JASSO criteria were used (HR = 1.51, 95% CI 1.04-2.21), but not when the NCEP-ATP III criteria were used (HR = 1.09, 95% CI 0.78-1.53). Metabolic risk factors, elevated fasting blood glucose, and MUHO were positively associated with cancer mortality (P <0.05). MetS diagnosed using the JASSO criteria and MUHO were associated with an increased risk of total cancer mortality in the Japanese population.
Fujii Ryosuke, Hishida Asahi, Nakatochi Masahiro, Tsuboi Yoshiki, Suzuki Koji, Kondo Takaaki, Ikezaki Hiroaki, Hara Megumi, Okada Rieko, Tamura Takashi, Shimoshikiryo Ippei, Suzuki Sadao, Koyama Teruhide, Kuriki Kiyonori, Takashima Naoyuki, Kokichi Arisawa, Momozawa Yukihide, Kubo Michiaki, Takeuchi Kenji and Wakai Kenji : Associations of genome-wide polygenic risk score and risk factors with hypertension in a Japanese population, Circulation. Genomic and Precision Medicine, Vol.15, No.4, e003612, 2022.
(要約)
Although many polygenic risk scores (PRS) for cardiovascular traits have been developed in European populations, it is an urgent task to construct a PRS and to evaluate its ability in non-European populations. We developed a genome-wide PRS for blood pressure in a Japanese population and examined the associations between this PRS and hypertension prevalence. We performed a cross-sectional study in 11 252 Japanese individuals who participated in the J-MICC (Japan Multi-Institutional Collaborative Cohort) study. Using publicly available GWAS summary statistics from Biobank Japan, we developed the PRS in the target data (n=7876). With >30 000 single nucleotide polymorphisms, we evaluated PRS performance in the test data (n=3376). Hypertension was defined as systolic blood pressure of 130 mm Hg or more, or diastolic blood pressure of 85 mm Hg or more, or taking an antihypertensive drug. Compared with the middle PRS quintile, the prevalence of hypertension at the top PRS quintile was higher independently from traditional risk factors (odds ratio, 1.73 [95% CI, 1.32-2.27]). The difference of mean systolic blood pressure and diastolic blood pressure between the middle and the top PRS quintile was 4.55 (95% CI, 2.26-6.85) and 2.32 (95% CI, 0.86-3.78) mm Hg, respectively. Subgroups reflecting combinations of Japanese PRS and modifiable lifestyles and factors (smoking, alcohol intake, sedentary time, and obesity) were associated with the prevalence of hypertension. A European-derived PRS was not associated with hypertension in our participants. A PRS for blood pressure was significantly associated with hypertension and BP traits in a general Japanese population. Our findings also highlighted the importance of a combination of PRS and risk factors for identifying high-risk subgroups.
(キーワード)
Cross-Sectional Studies / Genetic Predisposition to Disease / Genome-Wide Association Study / Humans / Hypertension / Japan / Multifactorial Inheritance / Risk Factors
Kayoko Koga, Megumi Hara, Chisato Shimanoe, Yuichiro Nishida, Takuma Furukawa, Chiharu Iwasaka, Keitaro Tanaka, Jun Otonari, Hiroaki Ikezaki, Yoko Kubo, Yasufumi Kato, Takashi Tamura, Asahi Hishida, Keitaro Matsuo, Hidemi Ito, Yohko Nakamura, Miho Kusakabe, Daisaku Nishimoto, Keiichi Shibuya, Sadao Suzuki, Miki Watanabe, Etsuko Ozaki, Daisuke Matsui, Kiyonori Kuriki, Naoyuki Takashima, Aya Kadota, Kokichi Arisawa, Sakurako Katsuura-Kamano, Kenji Takeuchi and Kenji Wakai : Association of perceived stress and coping strategies with the renal function in middleaged and older Japanese men and women, Scientific Reports, Vol.12, No.1, 291, 2022.
(要約)
Elucidating the risk factors for chronic kidney disease is important for preventing end-stage renal disease and reducing mortality. However, little is known about the roles of psychosocial stress and stress coping behaviors in deterioration of the renal function, as measured by the estimated glomerular filtration rate (eGFR). This cross-sectional study of middle-aged and older Japanese men (n = 31,703) and women (n = 38,939) investigated whether perceived stress and coping strategies (emotional expression, emotional support seeking, positive reappraisal, problem solving, and disengagement) were related to the eGFR, with mutual interactions. In multiple linear regression analyses adjusted for age, area, lifestyle factors, and psychosocial variables, we found a significant inverse association between perceived stress and the eGFR in men (P = 0.02), but not women. This male-specific inverse association was slightly attenuated after adjustment for the history of hypertension and diabetes and was more evident in lower levels of emotional expression (P = 0.003). Unexpectedly, problem solving in men (P < 0.001) and positive reappraisal in women (P = 0.002) also showed an inverse association with the eGFR. Perceived stress may affect the eGFR, partly through the development of hypertension and diabetes. The unexpected findings regarding coping strategies require the clarification of the underlying mechanisms, including the hormonal and immunological aspects.
(キーワード)
Adaptation, Psychological / Adult / Age Factors / Aged / Cross-Sectional Studies / Diabetes Mellitus / Emotions / Female / Glomerular Filtration Rate / Humans / Hypertension / Japan / Kidney / Male / Middle Aged / Problem Solving / Prospective Studies / Psychological Distress / Renal Insufficiency, Chronic / Risk Assessment / Risk Factors / Sex Factors / Social Support / Stress, Psychological
The aim of the present study was to investigate the associations between breastfeeding and the prevalence of metabolic syndrome in community-dwelling parous women and to clarify whether the associations depend on age. The present cross-sectional study included 11,118 women, aged 35-69 years. Participants' longest breastfeeding duration for one child and their number of breastfed children were assessed using a self-administered questionnaire, and their total breastfeeding duration was approximated as a product of the number of breastfed children and the longest breastfeeding duration. The longest and the total breastfeeding durations were categorized into none and tertiles above 0 months. Metabolic syndrome and cardiovascular risk factors (obesity, hypertension, dyslipidemia, and hyperglycemia) were defined as primary and secondary outcomes, respectively. Associations between breastfeeding history and metabolic syndrome or each cardiovascular risk factor were assessed using multivariable unconditional logistic regression analysis. Among a total of 11,118 women, 10,432 (93.8%) had ever breastfed, and 1,236 (11.1%) had metabolic syndrome. In participants aged <55 years, an inverse dose-response relationship was found between the number of breastfed children and the prevalence of metabolic syndrome; multivariable-adjusted odds ratios for 1, 2, 3, and ≥4 breastfed children were 0.60 (95% confidence interval [CI]: 0.31 to 1.17), 0.50 (95% CI: 0.29 to 0.87), 0.44 (95% CI: 0.24 to 0.84), and 0.35 (95% CI: 0.14 to 0.89), respectively. The longest and total breastfeeding durations of longer than 0 months were also associated with lower odds of metabolic syndrome relative to no breastfeeding history in participants aged <55 years. In contrast, all measures of breastfeeding history were not significantly associated with metabolic syndrome and cardiovascular risk factors in participants aged ≥55 years old. Breastfeeding history may be related to lower prevalence of metabolic syndrome in middle-aged parous women.
(キーワード)
Adult / Aged / Breast Feeding / Cardiovascular Diseases / Cross-Sectional Studies / Female / Humans / Independent Living / Japan / Metabolic Syndrome / Middle Aged / Prevalence / Surveys and Questionnaires
Takuma Furukawa, Yuichiro Nishida, Megumi Hara, Chisato Shimanoe, Kayoko Koga, Chiharu Iwasaka, Yasuki Higaki, Keitaro Tanaka, Ryoko Nakashima, Hiroaki Ikezaki, Asahi Hishida, Takashi Tamura, Yasufumi Kato, Yudai Tamada, Kietaro Matsuo, Hidemi Ito, Haruo Mikami, Miho Kusakabe, Rie Ibusuki, Keiichi Shibuya, Sadao Suzuki, Hiroko Nakagawa-Senda, Etsuko Ozaki, Daisuke Matsui, Kiyonori Kuriki, Yasuyuki Nakamura, Aya Kadota, Kokichi Arisawa, Sakurako Katsuura-Kamano, Kenji Takeuchi and Kenji Wakai : Effect of the interaction between physical activity and estimated macronutrient intake on HbA1c: population-based cross-sectional and longitudinal studies, BMJ Open Diabetes Research & Care, Vol.10, No.1, e002479, 2021.
(要約)
Healthy diet and physical activity (PA) are essential for preventing type 2 diabetes, particularly, a combination of diet and PA. However, reports on interaction between PA and diet, especially from large epidemiological studies, are limited. We investigated the effect of interaction between PA and macronutrient intake on hemoglobin A1c (HbA1c) levels in the general population. We conducted a cross-sectional study of 55 469 men and women without diabetes who participated in the baseline survey of the Japan Multi-Institutional Collaborative Cohort Study. A self-administered questionnaire ascertained PA and macronutrient intake (carbohydrate, fat, and protein). Multiple linear regression analyses were performed to adjust for confounding variables and examine the interactions. In addition, we conducted a longitudinal study during a 5-year period within a subcohort (n=6881) with accelerometer-assessed PA data. Overall, PA had a weak inverse association (β=-0.00033, p=0.049) and carbohydrate intake had a strong positive association (β=0.00393, p<0.001) with HbA1c. We observed a tendency of interactions between PA and carbohydrate or fat intake, but not protein intake, on HbA1c levels after adjusting for age, sex, study area, total energy intake, alcohol consumption, smoking, and medication for hypertension or hypercholesterolemia (P=0.054, 0.006, and 0.156, respectively). The inverse associations between PA and HbA1c level were more evident in participants with high-carbohydrate (or low-fat) intake than in participants with low-carbohydrate (or high-fat) intake. Although further adjustment for body mass index slightly attenuated the above interactions (P=0.098 for carbohydrate and 0.068 for fat), the associations between PA and HbA1c level in stratified analyses remained unchanged. Similar associations and interactions were reproduced in the longitudinal study. The present results suggest that the effect of PA on HbA1c levels is modified by intake of macronutrient composition.
(キーワード)
Cohort Studies / Cross-Sectional Studies / Diabetes Mellitus, Type 2 / Eating / Exercise / Female / Glycated Hemoglobin A / Humans / Longitudinal Studies / Male
Mizuki Ohashi, Katsuyuki Miura, Naoyuki Takashima, Aya Kadota, Yoshino Saito, Shunichiro Tsuji, Takashi Murakami, Yuka Kadomatsu, Mako Nagayoshi, Megumi Hara, Keitaro Tanaka, Takashi Tamura, Asahi Hishida, Toshiro Takezaki, Ippei Shimoshikiryo, Etsuko Ozaki, Isao Watanabe, Sadao Suzuki, Miki Watanabe, Kiyonori Kuriki, Kokichi Arisawa, Sakurako Katsuura-Kamano, Sho Yamasaki, Hiroaki Ikezaki, Isao Oze, Yuriko N. Koyanagi, Haruo Mikami, Yohko Nakamura, Kenji Takeuchi, Yoshikuni Kita and Kenji Wakai : The association of reproductive history with hypertension and obesity depending on menopausal status: the J-MICC Study, Hypertension Research, Vol.45, No.4, 708-714, 2021.
(要約)
Previous studies have reported that the number of pregnancies and childbirths affected the risk of cardiovascular diseases (CVDs). However, the influence of reproductive history on hypertension and obesity, which are important risk factors for CVDs, is still unclear. Moreover, this association may vary depending on menopausal status. We evaluated the association of reproductive history with hypertension and obesity using a large cross-sectional dataset from the Japan Multi-Institutional Collaborative Cohort Study (J-MICC Study). At the baseline survey, physical data, blood samples, and self-reported health questionnaires were collected. Participants with insufficient data were excluded, and 24,558 women from eight study regions were included in this study. Logistic regression analysis was conducted to evaluate the association of reproductive history with hypertension and obesity using multivariable-adjusted odds ratios. In premenopausal women, childbirth showed a generally protective effect on hypertension but not on obesity. In postmenopausal women, childbirth was positively associated with obesity and hypertension but not with hypertension after adjusting for BMI. In conclusion, reproductive history was associated with hypertension and obesity in a large Japanese population, and this association differed between premenopausal and postmenopausal women.
Sakurako Katsuura-Kamano, Kokichi Arisawa, Hirokazu Uemura, Tien Van Nguyen, Toshiro Takezaki, Rie Ibusuki, Sadao Suzuki, Takahiro Otani, Rieko Okada, Yoko Kubo, Takashi Tamura, Asahi Hishida, Teruhide Koyama, Daisuke Matsui, Kiyonori Kuriki, Naoyuki Takashima, Naoko Miyagawa, Hiroaki Ikezaki, Yuji Matsumoto, Yuichiro Nishida, Chisato Shimanoe, Isao Oze, Keitaro Matsuo, Haruo Mikami, Miho Kusakabe, Kenji Takeuchi, Kenji Wakai and the (J-MICC) Cohort Collaborative Multi-Institutional Japan Study : Association of skipping breakfast and short sleep duration with the prevalence of metabolic syndrome in the general Japanese population: baseline data from the Japan Multi-Institutional Collaborative Cohort Study, Preventive Medicine Reports, Vol.24, 101613, 2021.
(要約)
The purpose of the study was to investigate sex-specific associations of skipping breakfast and short sleep duration with metabolic syndrome (MetS) and their interaction. We analyzed baseline data of 14,907 men and 14,873 women aged 35-69 years, who participated in the Japan Multi-Institutional Collaborative Cohort Study from 2005. MetS was diagnosed using a modification of the National Cholesterol Education Program Adult Treatment Panel III revised definition (NCEP-R 2005), using body mass index instead of waist circumference. Breakfast consumption was classified into two categories: ≥6 days/week (consumers) or <6 days/week (skippers). Sleep duration was classified into three categories: <6h, 6 to <8 h, and ≥8 h/day. Multivariate logistic regression analysis was performed to estimate odds ratios (ORs) and 95 % confidence intervals (CIs) and examine the presence of interaction. In men, skipping breakfast and short sleep duration were independently associated with an increased prevalence of MetS (OR 1.26, 95%CI 1.12-1.42 and OR 1.28, 95%CI 1.12-1.45, respectively), obesity, and components of MetS. However, no significant interaction was observed between skipping breakfast and short sleep duration. In women, skipping breakfast and short sleep duration were associated with an increased prevalence of obesity, but not with MetS. These findings indicate that breakfast consumption and moderate sleep duration may be associated with a lower risk of MetS, particularly in men.
<p><b>Background:</b> Little is known about whether insufficient moderate-to-vigorous physical activity (MVPA) and longer sedentary behavior (SB) are independently associated with estimated glomerular filtration rate (eGFR) and chronic kidney disease (CKD), whether they interact with known risk factors for CKD, and the effect of replacing sedentary time with an equivalent duration of physical activity on kidney function.</p><p><b>Methods:</b> We examined the cross-sectional association of MVPA and SB with eGFR and CKD in 66,603 Japanese cohort study in 14 areas from 2004 to 2013. MVPA and SB were estimated using a self-reported questionnaire, and CKD was defined as eGFR <60 mL/min/1.73 m<sup>2</sup>. Multiple linear regression analyses, logistic regression analyses, and an isotemporal substitution model were applied.</p><p><b>Results:</b> After adjusting for potential confounders, higher MVPA and longer SB were independently associated with higher eGFR (<i>P</i> for trend MVPA <0.0001) and lower eGFR (<i>P</i> for trend SB <0.0001), and a lower odds ratio (OR) of CKD (adjusted OR of MVPA ≥20 MET·h/day, 0.76; 95% confidence interval [CI], 0.68-0.85 compared to MVPA <5 MET·h/day) and a higher OR of CKD (adjusted OR of SB ≥16 h/day, 1.81; 95% CI, 1.52-2.15 compared to SB <7 h/day), respectively. The negative association between MVPA and CKD was stronger in men, and significant interactions between sex and MVPA were detected. Replacing 1 hour of SB with 1 hour of physical activity was associated with about 3 to 4% lower OR of CKD.</p><p><b>Conclusions:</b> These findings indicate that replacing SB with physical activity may benefit kidney function, especially in men, adding to the possible evidence on CKD prevention.</p>
Mako Nagayoshi, Kenji Takeuchi, Yudai Tamada, Kato Yasufumi, Yoko Kubo, Rieko Okada, Takashi Tamura, Asahi Hishida, Jun Otonari, Hiroaki Ikezaki, Yuichiro Nishida, Chisato Shimanoe, Yuriko N. Koyanagi, Keitaro Matsuo, Mikami Haruo, Kusakabe Miho, Daisaku Nishimoto, Keiichi Shibuya, Sadao Suzuki, Takeshi Nishiyama, Etsuko Ozaki, Isao Watanabe, Kiyonori Kuriki, Naoyuki Takashima, Aya Kadota, Kokichi Arisawa, Sakurako Katsuura-Kamano, Kenji Wakai and the (J-MICC) Cohort Collaborative Multi-Institutional Japan Study : Sex-specific Relationship between Stress Coping Strategies and All-Cause Mortality: Japan Multi-Institutional Collaborative Cohort Study, Journal of Epidemiology, 2021.
(要約)
Stress coping strategies are related to health outcomes. However, there is no clear evidence for sex differences between stress-coping strategies and mortality. We investigated the relationship between all-cause mortality and stress-coping strategies, focusing on sex differences among Japanese adults. A total of 79,580 individuals aged 35-69 years participated in the Japan Multi-Institutional Collaborative Cohort Study between 2004 and 2014 and were followed up for mortality. The frequency of use of the five coping strategies was assessed using a questionnaire. Sex-specific, multivariable-adjusted hazard ratios (HRs) for using each coping strategy "sometimes," and "often/very often" (versus "very few" use) were computed for all-cause mortality. Furthermore, relationships were analyzed in specific follow-up periods when the proportion assumption was violated. During the follow-up (median: 8.5 years), 1,861 mortalities were recorded. In women, three coping strategies were related to lower total mortality. The HRs (95% confidence intervals) for "sometimes" were 0.81 (0.67-0.97) for emotional expression, 0.79 (0.66-0.95) for emotional support-seeking, and 0.80 (0.66-0.98) for disengagement. Men who "sometimes" used emotional expression and sometimes or often used problem-solving and positive reappraisal had a 15-41% lower HRs for all-cause mortality. However, those relationships were dependent on the follow-up period. There was evidence that sex modified the relationships between emotional support-seeking and all-cause mortality (p for interaction = 0.03). In a large Japanese population, selected coping strategies were associated with all-cause mortality. The relationship of emotional support-seeking was different between men and women.
Yusuke Kawamura, Akiyoshi Nakayama, Seiko Shimizu, Yu Toyoda, Yuichiro Nishida, Asahi Hishida, Sakurako Katsuura-Kamano, Kenichi Shibuya, Takashi Tamura, Makoto Kawaguchi, Satoko Suzuki, Satoko Iwasawa, Hiroshi Nakashima, Rie Ibusuki, Hirokazu Uemura, Megumi Hara, Kenji Takeuchi, Tappei Takada, Masashi Tsunoda, Kokichi Arisawa, Toshiro Takezaki, Keitaro Tanaka, Kimiyoshi Ichida, Kenji Wakai, Nariyoshi Shinomiya and Hirotaka Matsuo : A Proposal For Practical Diagnosis Of Renal Hypouricemia: Evidenced From Genetic Studies Of Nonfunctional Variants Of URAT1/SLC22A12 Among 30,685 Japanese Individuals, Biomedicines, Vol.9, No.8, 2021.
(要約)
Renal hypouricemia (RHUC) is characterized by a low serum uric acid (SUA) level and high fractional excretion of uric acid (FE). Further studies on FE in hypouricemic individuals are needed for a more accurate diagnosis of RHUC. In 30,685 Japanese health-examination participants, we genotyped the two most common nonfunctional variants of (NFV-), W258X (rs121907892) and R90H (rs121907896), in 1040 hypouricemic individuals (SUA ≤ 3.0 mg/dL) and 2240 individuals with FE data. The effects of NFV- on FE and SUA were also investigated using linear and multiple regression analyses. Frequency of hypouricemic individuals (SUA ≤ 3.0 mg/dL) was 0.97% (male) and 6.94% (female) among 30,685 participants. High frequencies of those having at least one allele of NFV- were observed in 1040 hypouricemic individuals. Furthermore, NFV- significantly increased FE and decreased SUA, enabling FE and SUA levels to be estimated. Conversely, FE and SUA data of hypouricemic individuals are revealed to be useful to predict the number of NFV-. Our findings reveal that specific patterns of FE and SUA data assist with predicting the number of nonfunctional variants of causative genes for RHUC, and can also be useful for practical diagnosis of RHUC even before genetic tests.
Yora Nindita, Masahiro Nakatochi, Rie Ibusuki, Ippei Shimoshikiryo, Daisaku Nishimoto, Keiichi Shimatani, Toshiro Takezaki, Hiroaki Ikezaki, Masayuki Murata, Megumi Hara, Yuichiro Nishida, Takashi Tamura, Asahi Hishida, Mako Nagayoshi, Rieko Okada, Keitaro Matsuo, Hidemi Ito, Haruo Mikami, Yohko Nakamura, Takahiro Otani, Sadao Suzuki, Teruhide Koyama, Etsuko Ozaki, Kiyonori Kuriki, Naoyuki Takashima, Naoko Miyagawa, Kokichi Arisawa, Sakurako Katsuura-Kamano, Yukihide Momozawa, Michiaki Kubo, Kenji Takeuchi, Kenji Wakai and the Study Cohort Collaborative Multi-Institutional Japan Group : Population-Based Impact of Smoking, Drinking, and Genetic Factors on HDL-Cholesterol Levels in J-MICC Study Participants, Journal of Epidemiology, 2021.
(要約)
Environmental and genetic factors are suggested to exhibit factor-based association with HDL-cholesterol (HDL-C) levels. However, the population-based effects of environmental and genetic factors have not been compared clearly. We conducted a cross-sectional study using data from the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study to evaluate the population-based impact of smoking, drinking, and genetic factors on low HDL-C. Data from 11,498 men and women aged 35-69 years were collected for a genome-wide association study (GWAS). Sixty-five HDL-C-related SNPs with genome-wide significance (P < 5 × 10) were selected from the GWAS catalog, and seven representative SNPs were defined, and the population-based impact was estimated using population attributable fraction (PAF). We found that smoking, drinking, daily activity, habitual exercise, egg intake, BMI, age, sex and the SNPs CETP rs3764261, APOA5 rs662799, LIPC rs1800588, LPL rs328, ABCA1 rs2575876, LIPG rs3786247, and APOE rs429358 were associated with HDL-C levels. The gene-environmental interactions on smoking and drinking were not statistically significant. The PAF for low HDL-C was the highest in men (63.2%) and in rs3764261 (31.5%) of the genetic factors, and the PAFs of smoking and drinking were 23.1% and 41.8%, respectively. The present study showed that the population-based impact of genomic factor CETP rs3764261 for low HDL-C was higher than that of smoking and lower than that of drinking.
Teruhide Koyama, Etsuko Ozaki, Nagato Kuriyama, Satomi Tomida, Tamami Yoshida, Ritei Uehara, Keitaro Tanaka, Megumi Hara, Asahi Hishida, Rieko Okada, Yoko Kubo, Isao Oze, Yuriko Koyanagi, Haruo Mikami, Yohko Nakamura, Ippei Shimoshikiryo, Toshiro Takezaki, Sadao Suzuki, Takahiro Otani, Kiyonori Kuriki, Naoyuki Takashima, Aya Kadota, Kokichi Arisawa, Sakurako Katsuura-Kamano, Hiroaki Ikezaki, Masayuki Murata, Kenji Takeuchi and Kenji Wakai : Effect of Underlying Cardiometabolic Diseases on the Association Between Sedentary Time and All-cause Mortality in a Large Japanese Population: A Cohort Analysis Based on the J-MICC Study, Journal of the American Heart Association, Vol.10, No.13, e018293, 2021.
(要約)
Background This study aimed to determine the association between sedentary time and mortality with regard to leisure-time physical activity with or without cardiometabolic diseases such as hypertension, dyslipidemia, and diabetes mellitus. Methods and Results Using data from the J-MICC (Japan Multi-Institutional Collaborative Cohort) Study, 64 456 participants (29 022 men, 35 434 women) were analyzed. Hazard ratios (HRs) and 95% CIs were used to characterize the relative risk of all-cause mortality to evaluate its association with sedentary time (categorical variables: <5, 5 to <7, 7 to <9, ≥9 h/d and 2-hour increments in exposure) according to the self-reported hypertension, dyslipidemia, and diabetes mellitus using a Cox proportional hazards model. A total of 2257 participants died during 7.7 years of follow-up. The corresponding HRs for each 2-hour increment in sedentary time among participants with all factors, no factors, hypertension, dyslipidemia, and diabetes mellitus were 1.153 (95% CI, 1.114-1.194), 1.125 (95% CI, 1.074-1.179), 1.202 (95% CI, 1.129-1.279), 1.176 (95% CI, 1.087-1.273), and 1.272 (95% CI, 1.159-1.396), respectively. Furthermore, when analyzed according to the combined different factors (hypertension, dyslipidemia, and diabetes mellitus), HRs increased with each additional factor, and participants reporting all 3 conditions had the highest HR of 1.417 (95% CI, 1.162-1.728) independently of leisure-time metabolic equivalents. Conclusions The association between sedentary time and increased mortality is stronger among patients with hypertension, dyslipidemia, and diabetes mellitus regardless of leisure-time physical activity in a large Japanese population.
Tetsuya Matsuura, Yuki Takata, Toshiyuki Iwame, Jyoji Iwase, Kenji Yokoyama, Shoichiro Takao, Susumu Nishio, Kokichi Arisawa and Koichi Sairyo : Limiting the Pitch Count in Youth Baseball Pitchers Decreases Elbow Pain., Orthopaedic Journal of Sports Medicine, Vol.9, No.3, 2021.
(要約)
A pitch count limit of 70 pitches per day for baseball pitchers 12 years could be more protective against elbow pain and reduced flexion than a limit of 7 innings per day, but it may not be effective for reducing the risk of capitellar OCD.
Fujii Ryosuke, Hishida Asahi, Nishiyama Takeshi, Nakatochi Masahiro, Matsuo Keitaro, Ito Hidemi, Nishida Yuichiro, Shimanoe Chisato, Nakamura Yasuyuki, Turin Chowdhury Tanvir, Suzuki Sadao, Watanabe Miki, Ibusuki Rie, Takezaki Toshiro, Mikami Haruo, Nakamura Yohko, Ikezaki Hiroaki, Murata Masayuki, Kuriki Kiyonori, Kuriyama Nagato, Matsui Daisuke, Kokichi Arisawa, Sakurako Katsuura-Kamano, Tsukamoto Mineko, Tamura Takashi, Kubo Yoko, Kondo Takaaki, Momozawa Yukihide, Kubo Michiaki, Takeuch Kenji, Wakai Kenji and Group Study J-MICC : Assessing the relationship between high-sensitivity C-reactive protein and kidney function employing mendelian randomization in a Japanese community based J-MICC Study, Journal of Epidemiology, 2021.
(要約)
Inflammation is thought to be a risk factor for kidney disease. However, discussion is controversial whether inflammatory status is either a cause or an outcome of chronic kidney disease. We aimed to investigate the causal relationship between high-sensitivity C-reactive protein (hs-CRP) and estimated glomerular filtration rate (eGFR) using mendelian randomization (MR) approaches. A total of 10,521 participants of the Japan Multi-institutional Collaborative Cohort Study was analyzed in this study. We used two-sample MR approaches (the inverse-variance weighted (IVW), the weighted median (WM), and the MR-Egger method) to estimate the effect of genetically determined hs-CRP on kidney function. We selected four and three hs-CRP associated single nucleotide polymorphisms (SNPs) as two instrumental variables (IV): IV and IV, based on SNPs previously identified in European and Asian populations. IV and IV explained 3.4% and 3.9% of the variation in hs-CRP, respectively. Using the IV, genetically determined hs-CRP was not significantly associated with eGFR in the IVW and the WM methods (estimate per 1 unit increase in ln(hs-CRP), 95%CI: 0.000, -0.019 to 0.020 and -0.003, -0.019 to 0.014). For IV, we found similar results using the IVW and the WM methods (estimate, 95% CI: -0.005, -0.020 to 0.010 and -0.004, -0.020 to 0.012). The MR-Egger method also showed no causal relationships between hs-CRP and eGFR (IV: -0.008, -0.058 to 0.042; IV: 0.001, -0.036 to 0.036). Our two-sample MR analyses with different IVs did not support a causal effect of hs-CRP on eGFR.
Van Tien Nguyen, Kokichi Arisawa, Hirokazu Uemura, Naomi Imaeda, Chiho Goto and Sakurako Katsuura-Kamano : Association between nutrient patterns and fatty liver index: Baseline survey of the Japan Multi-Institutional Collaborative Cohort Study in Tokushima, Japan, Journal of Epidemiology, Vol.32, No.8, 376-383, 2021.
(要約)
The fatty liver index (FLI) is a good non-invasive approach for fatty liver disease diagnosis. The objective of this study was to examine the associations of nutrient patterns with nonalcoholic fatty liver disease (NAFLD) in a Japanese population. A total of 1,588 subjects (789 men and 799 women) aged 35 to 69 years were recruited in the baseline survey of the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study in Tokushima Prefecture. Factor analysis was applied to energy-adjusted intake of 21 nutrients, and nutrient patterns were extracted. Multiple logistic regression analysis was used to analyze the relationships between nutrient patterns and the high FLI category (60). Four nutrient patterns were extracted: Factor 1, vitamins, dietary fiber, iron and potassium pattern; Factor 2, fats and fat-soluble vitamins pattern; Factor 3, saturated fat, calcium, vitamin B and low carbohydrate pattern; and Factor 4, sodium, protein and vitamin D pattern. After adjustment for sex, age, and other potential confounding variables, higher Factor 1 scores were significantly associated with lower odds ratios of NAFLD (P for trend <0.05). Analysis of each component of FLI showed that there were significant inverse associations between Factor 1 scores and high body mass index and large waist circumference. The present findings suggest that a nutrient pattern rich in vitamins, fiber, iron, and potassium was associated with lower prevalence of NAFLD in a Japanese population. Obesity and abdominal obesity may be intermediate variables for the association between this nutrient pattern and NAFLD.
Traditional observational studies have reported a positive association between higher body mass index (BMI) and the risk of colorectal cancer (CRC). However, evidence from other approaches to pursue the causal relationship between BMI and CRC is sparse. A two-sample Mendelian randomization (MR) study was undertaken using 68 single nucleotide polymorphisms (SNPs) from the Japanese genome-wide association study (GWAS) and 654 SNPs from the GWAS catalogue for BMI as sets of instrumental variables. For the analysis of SNP-BMI associations, we undertook a meta-analysis with 36 303 participants in the Japanese Consortium of Genetic Epidemiology studies (J-CGE), comprising normal populations. For the analysis of SNP-CRC associations, we utilized 7636 CRC cases and 37 141 controls from five studies in Japan, and undertook a meta-analysis. Mendelian randomization analysis of inverse-variance weighted method indicated that a one-unit (kg/m ) increase in genetically predicted BMI was associated with an odds ratio of 1.13 (95% confidence interval, 1.06-1.20; P value <.001) for CRC using the set of 68 SNPs, and an odds ratio of 1.07 (1.03-1.11, 0.001) for CRC using the set of 654 SNPs. Sensitivity analyses robustly showed increased odds ratios for CRC for every one-unit increase in genetically predicted BMI. Our MR analyses strongly support the evidence that higher BMI influences the risk of CRC. Although Asians are generally leaner than Europeans and North Americans, avoiding higher BMI seems to be important for the prevention of CRC in Asian populations.
(キーワード)
Aged / Body Mass Index / Case-Control Studies / Colorectal Neoplasms / Female / Genetic Predisposition to Disease / Genome-Wide Association Study / Humans / Japan / Male / Mendelian Randomization Analysis / Middle Aged / Odds Ratio / Polymorphism, Single Nucleotide / Risk Factors
H Suzuki, Y Nakamura, K Matsuo, N Imaeda, C Goto, A Narita, A Shimizu, N Takashima, K Matsui, K Miura, M Nakatochi, A Hishida, T Tamura, Y Kadomatsu, R Okada, Y Nishida, C Shimanoe, D Nishimoto, T Takezaki, I Oze, H Ito, H Ikezaki, M Murata, D Matsui, E Ozaki, H Mikami, Y Nakamura, S Suzuki, M Watanabe, Kokichi Arisawa, H Uemura, K Kuriki, Y Momozawa, M Kubo, Y Kita, K Takeuchi and K Wakai : A genome-wide association study in Japanese identified one variant associated with a preference for a Japanese dietary pattern, European Journal of Clinical Nutrition, 2020.
(要約)
Individual eating habits may be influenced by genetic factors, in addition to environmental factors. Previous studies suggested that adherence to Japanese food patterns was associated with a decreased risk of all-cause and cardiovascular disease mortality. We conducted a genome-wide association study (GWAS) in a Japanese population to find genetic variations that affect adherence to a Japanese food pattern. We analyzed GWAS data using 14,079 participants from the Japan Multi-Institutional Collaborative Cohort study. We made a Japanese food score based on six food groups. Association of the imputed variants with the Japanese food score was performed by linear regression analysis with adjustments for age, sex, total energy intake, alcohol intake (g/day), and principal components 1-10 omitting variants in the major histocompatibility region. We found one SNP in the 14q11.2 locus that was significantly associated with the Japanese food score with P values <5 × 10. Functional annotation revealed that the expression levels of two genes (BCL2L2, SLC22A17) were significantly inversely associated with this SNP. These genes are known to be related to olfaction and obesity. We found a new SNP that was associated with the Japanese food score in a Japanese population. This SNP is inversely associated with genes link to olfaction and obesity.
Takashi Tamura, Nagato Kuriyama, Teruhide Koyama, Etsuko Ozaki, Daisuke Matsui, Yuka Kadomatsu, Mineko Tsukamoto, Yoko Kubo, Rieko Okada, Asahi Hishida, Tae Sasakabe, Sayo Kawai, Mariko Naito, Naoyuki Takashima, Aya Kadota, Keitaro Tanaka, Megumi Hara, Sadao Suzuki, Hiroko Nakagawa-Senda, Toshiro Takezaki, Ippei Shimoshikiryo, Hiroaki Ikezaki, Masayuki Murata, Isao Oze, Hidemi Ito, Haruo Mikami, Yohko Nakamura, Kiyonori Kuriki, Kokichi Arisawa, Hirokazu Uemura, Kenji Takeuchi and Kenji Wakai : Association between plasma levels of homocysteine, folate, and vitamin B12, and dietary folate intake and hypertension in a cross-sectional study, Scientific Reports, Vol.10, No.1, 18499, 2020.
(要約)
There are few studies examining the association between homocysteine (Hcy) level and the risk of hypertension with consideration for folate and vitamin B as related to Hcy level. We simultaneously examined the associations of plasma levels of Hcy, folate, and vitamin B, and dietary folate intake with the prevalence of hypertension. Participants included 1046 men and 1033 women (mean age ± standard deviation: 56.0 ± 8.9 years) in the Japan Multi-Institutional Collaborative Cohort Study. Dietary folate intake was estimated using a validated food frequency questionnaire. Hypertension was defined based on measured blood pressure and use of antihypertensive medication. A total of 734 participants (35.3%) had hypertension. Multivariate-adjusted odds ratios of hypertension for the highest quartile group of Hcy were 2.36 (95% CI 1.41-3.96) in men and 1.86 (95% CI 1.11-3.11) in women, as compared with the lowest group (P for trend = 0.014 and 0.005, respectively). Dietary folate intake was not correlated with hypertension in both men and women (P for trend = 0.099 and 0.703, respectively). Plasma vitamin B was positively associated with hypertension only in women (P for trend = 0.027). Plasma Hcy level was positively linked with hypertension after controlling for covariates, including folate and vitamin B.
I Shimoshikiryo, R Ibusuki, K Shimatani, D Nishimoto, T Takezaki, Y Nishida, C Shimanoe, A Hishida, T Tamura, R Okada, Y Kubo, E Ozaki, D Matsui, S Suzuki, H Nakagawa-Senda, K Kuriki, Y Kita, N Takashima, Kokichi Arisawa, H Uemura, H Ikezaki, N Furusyo, I Oze, YN Koyanagi, H Mikami, Y Nakamura, M Naito and K Wakai : Association between alcohol intake pattern and metabolic syndrome components and simulated change by alcohol intake reduction: A cross-sectional study from the Japan Multi-Institutional Collaborative Cohort Study, Alcohol, Vol.S0741-8329, No.20, 30284-6, 2020.
The Japan Multi-institutional Collaborative Cohort (J-MICC) study was launched in 2005 to examine gene-environment interactions in lifestyle-related diseases, including cancers, among the Japanese. This report describes the study design and baseline profile of the study participants. The participants of the J-MICC Study were individuals aged 35 to 69 years enrolled from respondents to study announcements in specified regions, inhabitants attending health checkup examinations provided by local governments, visitors at health checkup centers, and first-visit patients at a cancer hospital in Japan. At the time of the baseline survey, from 2005 to 2014, we obtained comprehensive information regarding demographics, education, alcohol consumption, smoking, sleeping, exercise, food intake frequency, medication and supplement use, personal and family disease history, psychological stress, and female reproductive history, and collected peripheral blood samples. The baseline survey included 92,610 adults (mean age: 55.2 [9.4] years, 44.1% men) from 14 study regions in 12 prefectures. The participation rate was 33.5%, with participation ranging from 19.7% to 69.8% in different study regions. The largest number of participants was in the age groups of 65-69 years for men and 60-64 years for women. There were differences in body mass index, educational attainment, alcohol consumption, smoking, and sleep duration between men and women. The J-MICC Study collected lifestyle and clinical data and biospecimens from over 90,000 participants. This cohort is expected to be a valuable resource for the national and international scientific community in providing evidence to support longer healthy lives.
(キーワード)
Adult / Aged / Alcohol Drinking / Cohort Studies / Female / Humans / Japan / Life Style / Male / Middle Aged / Surveys and Questionnaires
Genome-wide association studies provided many biological insights into coronary artery disease (CAD), but these studies were mainly performed in Europeans. Genome-wide association studies in diverse populations have the potential to advance our understanding of CAD. We conducted 2 genome-wide association studies for CAD in the Japanese population, which included 12 494 cases and 28 879 controls and 2808 cases and 7261 controls, respectively. Then, we performed transethnic meta-analysis using the results of the coronary artery disease genome-wide replication and meta-analysis plus the coronary artery disease 1000 Genomes meta-analysis with UK Biobank. We then explored the pathophysiological significance of these novel loci and examined the differences in CAD-susceptibility loci between Japanese and Europeans. We identified 3 new loci on chromosome 1q21 (), 10q26 (), and 11q22 (-). Quantitative trait locus analyses suggested the association of and - with atherosclerotic immune cells. Tissue/cell type enrichment analysis showed the involvement of arteries, adrenal glands, and fat tissues in the development of CAD. We next compared the odds ratios of lead variants for myocardial infarction at 76 genome-wide significant loci in the transethnic meta-analysis and a moderate correlation between Japanese and Europeans, where 8 loci showed a difference. Finally, we performed tissue/cell type enrichment analysis using East Asian-frequent and European-frequent variants according to the risk allele frequencies and identified significant enrichment of adrenal glands in the East Asian-frequent group while the enrichment of arteries and fat tissues was found in the European-frequent group. These findings indicate biological differences in CAD susceptibility between Japanese and Europeans. We identified 3 new loci for CAD and highlighted the genetic differences between the Japanese and European populations. Moreover, our transethnic analyses showed both shared and unique genetic architectures between the Japanese and Europeans. While most of the underlying genetic bases for CAD are shared, further analyses in diverse populations will be needed to elucidate variations fully.
(キーワード)
Asian People / Chromosomes, Human / Coronary Artery Disease / Female / Genetic Loci / Genome-Wide Association Study / Humans / Japan / Male / Meta-Analysis as Topic / United Kingdom / White People
Kokichi Arisawa, Sakurako Katsuura-Kamano, Hirokazu Uemura, Nguyen Van Tien, Asahi Hishida, Takashi Tamura, Yoko Kubo, Mineko Tsukamoto, Keitaro Tanaka, Megumi Hara, Toshiro Takezaki, Daisaku Nishimoto, Teruhide Koyama, Etsuko Ozaki, Sadao Suzuki, Takeshi Nishiyama, Kiyonori Kuriki, Aya Kadota, Naoyuki Takashima, Hiroaki Ikezaki, Masayuki Murata, Isao Oze, Keitaro Matsuo, Haruo Mikami, Yohko Nakamura, Kenji Takeuchi and Kenji Wakai : Association of dietary acid load with the prevalence of metabolic syndrome among participants in the baseline survey of the Japan Multi-Institutional Collaborative Cohort Study, Nutrients, Vol.12, No.6, 1605, 2020.
(要約)
The association between dietary acid load and metabolic syndrome (MetS) has not been fully investigated. A cross-sectional study was performed on 14,042 men and 14,105 women (aged 35-69 years) who participated in a baseline survey of the Japan Multi-Institutional Collaborative Cohort study. Dietary acid load was assessed using the net-endogenous-acid-production (NEAP) score that is closely correlated with the rate of renal net acid excretion. MetS was diagnosed according to the Joint Interim Statement Criteria of 2009 using body-mass index instead of waist circumference. After adjusting for potential confounders, higher NEAP scores were associated with a significantly increased odds ratio (OR) of MetS, obesity, high blood pressure, and high fasting blood glucose. These associations remained significant after further adjustment for carbohydrate intake or two nutrient-pattern scores significantly associated with MetS. After adjustment for fiber, iron, potassium, and vitamin pattern scores, the OR of MetS for the highest quartile of NEAP scores, relative to the lowest quartile, was 1.25 (95% confidence interval 1.12-1.39). There was no significant interaction between sex, age, or body-mass index and NEAP. Higher dietary acid load was associated with a higher prevalence of MetS and several of its components, independently of carbohydrate intake or nutrient patterns.
(キーワード)
Metabolic syndrome / Dietary acid load / Net endogenous acid production / Cross-sectional study
Rieko Okada, Yuka Kadomatsu, Mineko Tsukamoto, Tae Sasakabe, Sayo Kawai, Takashi Tamura, Asahi Hishida, Hiroaki Ikezaki, Norihiro Furusyo, Keitaro Tanaka, Megumi Hara, Sadao Suzuki, Miki Watanabe, Toshiro Takezaki, Daisaku Nishimoto, Daisuke Matsui, Isao Watanabe, Kiyonori Kuriki, Naoyuki Takashima, Yasuyuki Nakamura, Sakurako Katsuura-Kamano, Kokichi Arisawa, Haruo Mikami, Yoko Nakamura, Isao Oze, Yuriko N. Koyanagi, Mariko Naito, Kenji Wakai and Study Multi-Institutional Collaborative Cohort (J-MICC) Japan : Combined effect of weight gain within normal weight range and parental hypertension on the prevalence of hypertension; from the J-MICC Study., Journal of Human Hypertension, Vol.34, No.2, 125-131, 2020.
(要約)
The aim of this study is to show the combined effect of weight gain within normal weight range in adulthood and parental HT on the prevalence of HT. The study subjects were 44,998 individuals (19,039 men and 25,959 women) with normal weight (body mass index [BMI] 18.5-24.9) aged 35-69 years who participated in the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study. They were categorized into six groups by weight gain from age 20 years (<10 kg, and ≥10 kg) and by the number of parents having HT (no parent, one parent, and both parents). Odds ratios for HT were estimated after adjustment for age, sex, current BMI, estimated daily sodium intake, and other confounding factors. The prevalence of HT (31.5% in total subjects) gradually increased with greater weight gain from age 20 years and with greater number of parents with HT. Subjects who gained weight ≥10 kg and having both parents with HT showed the highest risk of having HT compared with those who gained weight <10 kg without parental HT (59.8% vs. 24.9%, odds ratio 4.25, 95% CI 3.53-5.13 after adjustment). This association was similarly observed in any category of age, sex, and BMI. Subjects who gained weight within normal range of BMI and having one or both parent(s) with HT showed the higher risk of having HT independent of their attained BMI in their middle ages. Thus, subjects having parent(s) with HT should avoid gaining their weight during adulthood, even within normal range of BMI, to reduce the risk of having HT.
K Sakai, C Tanikawa, A Hirasawa, T Chiyoda, W Yamagami, F Kataoka, N Susumu, C Terao, Y Kamatani, A Takahashi, Y Momozawa, M Hirata, M Kubo, N Fuse, T Takai-Igarashi, A Shimizu, A Fukushima, A Kadota, Kokichi Arisawa, H Ikezaki, K Wakai, T Yamaji, N Sawada, M Iwasaki, S Tsugane, D Aoki and K Matsuda : Identification of a novel uterine leiomyoma GWAS locus in a Japanese population., Scientific Reports, Vol.10, No.1, 1197, 2020.
(要約)
Uterine leiomyoma is one of the most common gynaecologic benign tumours, but its genetic basis remains largely unknown. Six previous GWAS identified 33 genetic factors in total. Here, we performed a two-staged GWAS using 13,746 cases and 70,316 controls from the Japanese population, followed by a replication analysis using 3,483 cases and 4,795 controls. The analysis identified 9 significant loci, including a novel locus on 12q23.2 (rs17033114, P = 6.12 × 10 with an OR of 1.177 (1.141-1.213), LINC00485). Subgroup analysis indicated that 5 loci (3q26.2, 5p15.33, 10q24.33, 11p15.5, 13q14.11) exhibited a statistically significant effect among multiple leiomyomas, and 2 loci (3q26.2, 10q24.33) exhibited a significant effect among submucous leiomyomas. Pleiotropic analysis indicated that all 9 loci were associated with at least one proliferative disease, suggesting the role of these loci in the common neoplastic pathway. Furthermore, the risk T allele of rs2251795 (3q26.2) was associated with longer telomere length in both normal and tumour tissues. Our findings elucidated the significance of genetic factors in the pathogenesis of leiomyoma.
Tetsuya Matsuura, E Chosa, T Tajika, T Masatomi, S Arimitsu, A Yamamoto, M Nagasawa, Kokichi Arisawa and K Takagishi : Correlation between playing position, elbow physical findings and elbow pain in elementary school baseball players: Results of a multi-regional study in Japan., Journal of Orthopaedic Science, Vol.25, No.1, 122-126, 2020.
(要約)
Elbow injuries are common in young baseball players and evaluating the characteristics of young baseball players in a large-scale population is necessary. However, few studies have compared playing position, length of baseball experience, physical findings, and elbow pain in young baseball players. This retrospective multi-regional cohort study sought to document the physical findings at the elbow in Japanese elementary school baseball players and to examine the relationship between playing position, length of baseball experience, physical findings at the elbow, and elbow pain. In 2014, 720 fifth-grade baseball players from four regions in Japan were invited to participate in a questionnaire survey and undergo physical examination to obtain data on position played, length of baseball experience, presence of elbow pain, and physical findings at the elbow, including range of motion, tenderness, and valgus stress test results. Potential risk factors associated with elbow pain and correlations between physical findings and playing position, length of baseball experience, and elbow pain were investigated. The 720 subjects had a mean age of 10.4 years and 29.4% reported having experienced elbow pain for ≥1 week. Risk factors for elbow pain included playing pitcher and catcher, playing pitcher and fielder, and length of baseball experience. The most frequent finding was limitation of flexion (21.1%) followed by tenderness of the medial epicondyle (18.3%) and a positive valgus stress test (14.3%). These three findings were also significantly associated with elbow pain. Elbow extension was limited in 14.9% of subjects but there was no correlation with length of baseball experience or elbow pain. Our data show that elementary school baseball players who experienced elbow pain are likely to have valgus stress overload. Elbow pain might be prevented by not playing pitcher and catcher.
Y Usui, K Matsuo, I Oze, T Ugai, Y Koyanagi, Y Maeda, H Ito, A Hishida, K Takeuchi, T Tamura, M Tsukamoto, Y Kadomatsu, M Hara, Y Nishida, I Shimoshikiryo, T Takezaki, E Ozaki, D Matsui, I Watanabe, S Suzuki, M Watanabe, H Nakagawa-Senda, H Mikami, Y Nakamura, Kokichi Arisawa, Hirokazu Uemura, K Kuriki, N Takashima, A Kadota, H Ikezaki, M Murata, M Nakatochi, Y Momozawa, M Kubo and K Wakai : Impact of PSCA polymorphisms on the risk of duodenal ulcer., Journal of Epidemiology, JE20190184, 2019.
The first ever genome-wide association study (GWAS) of clinically defined gout cases and asymptomatic hyperuricaemia (AHUA) controls was performed to identify novel gout loci that aggravate AHUA into gout. We carried out a GWAS of 945 clinically defined gout cases and 1003 AHUA controls followed by 2 replication studies. In total, 2860 gout cases and 3149 AHUA controls (all Japanese men) were analysed. We also compared the ORs for each locus in the present GWAS (gout vs AHUA) with those in the previous GWAS (gout vs normouricaemia). This new approach enabled us to identify two novel gout loci (rs7927466 of and rs9952962 of ) and one suggestive locus (rs12980365 of ) at the genome-wide significance level (p<5.0 10). The present study also identified the loci of , and . One of them, rs671 of , was identified as a gout locus by GWAS for the first time. Comparing ORs for each locus in the present versus the previous GWAS revealed three 'gout vs AHUA GWAS'-specific loci (, and ) to be clearly associated with mechanisms of gout development which distinctly differ from the known gout risk loci that basically elevate serum uric acid level. This meta-analysis is the first to reveal the loci associated with crystal-induced inflammation, the last step in gout development that aggravates AHUA into gout. Our findings should help to elucidate the molecular mechanisms of gout development and assist the prevention of gout attacks in high-risk AHUA individuals.
R Fujii, A Hishida, M Nakatochi, N Furusyo, M Murata, K Tanaka, C Shimanoe, S Suzuki, M Watanabe, N Kuriyama, T Koyama, T Takezaki, I Shimoshikiryo, Kokichi Arisawa, Sakurako Katsuura-Kamano, N Takashima, TC Turin, K Kuriki, K Endoh, H Mikami, Y Nakamura, I Oze, H Ito, M Kubo, Y Momozawa, T Kondo, M Naito and K Wakai : Association of genetic risk score and chronic kidney disease in a Japanese population, Nephrology, Vol.24, No.6, 670-673, 2019.
(要約)
Chronic kidney disease (CKD) is a public health problem worldwide including Japan. Recent genome-wide association studies have discovered CKD susceptibility variants. We developed a genetic risk score (GRS) based on CKD-associated variants and assessed a possibility that the GRS can improve the discrimination capability for the prevalence of CKD in a Japanese population. The present study consists of 11 283 participants randomly selected from 12 Japan Multi-Institutional Collaborative Cohort Study sites. Individual GRS was constructed combining 18 single-nucleotide polymorphisms identified in a Japanese population. Participants with eGFR <60 mL/min per 1.73 m was defined as case (stage 3 CKD or higher) in this study. Logistic regression analysis was used to examine the association between the GRS and CKD risk with adjustment for sex, age, hypertension and type 2 diabetes mellitus. The frequency of individuals with CKD was 8.3%, which was relatively low compared with those previously reported in a Japanese population. The odds ratio of having CKD was 1.120 (95% confidence interval: 1.042-1.203) per 10 GRS increment in the fully adjusted model (P = 0.002). The C-statistic was significantly increased in the model with the GRS, comparing with the model without the GRS (0.720 vs 0.719, P = 0.008). Increment of the GRS was associated with increased risk of CKD. Additionally, the GRS significantly improved the discriminatory ability of CKD prevalence in a Japanese population; however, the improvement of discriminatory ability brought about by the GRS seemed to be small compared with that of non-genetic CKD risk factors.
Makoto Irahara, Wakako Shinahara, Mayumi Sugimoto, Yukiko Ogawa, Keiji Shitsukawa, Kenji Kubota, Limin Yang, Yukihiro Ohya, Hirohisa Saito, Shoji Kagami, Kokichi Arisawa and Hiroshi Kido : Trajectories of class-switching-related egg and cow's milk allergen-specific immunoglobulin isotype formation and its modification by eczema with low- and high-affinity immunoglobulin E during early infancy, Immunity, Inflammation and Disease, Vol.7, No.2, 74-85, 2019.
(要約)
Allergen-specific immunoglobulin isotype formation associated with immunoglobulin class-switching during the lactation period is the immunological background for food allergy in infants. We analyzed the serial changes in the production of feeding type-related egg- and milk-specific immunoglobulin isotypes from birth to 6 months of age with or without eczema in 84 infants. Allergen-specific immunoglobulin G1 (IgG1), IgG2, IgG3, IgG4, IgA, and IgE levels of hen's egg and bovine milk were measured in cord blood and blood samples from infants at 2, 4, and 6 months of age by the densely carboxylated protein microarray. Formula and mixed feeding were associated with a rapid increase in cow's milk allergen-specific immunoglobulins and feeding type-related significant differences in casein-specific immunoglobulin levels were detected. Breast and mixed feeding were associated with slow but significant increase in ovalbumin-specific IgG1 and IgE levels, but not other immunoglobulins. We found two different immunoglobulin isotype formation at 6 months of age with low- or high-affinity IgE against ovalbumin. One isotype formation pattern had relatively high ovalbumin-specific IgG1 levels, detectable IgG2, and low-affinity IgE, while the other had low ovalbumin-specific IgG1 levels, undetectable IgG2, and high levels of high-affinity IgE. The incidence of eczema was significantly higher in the latter pattern (84.6%), compared with the remaining infants (42.2%). Feeding practice-related allergen sensitization and immunoglobulin isotype formation were identified during the lactation period. The development of eczema during the lactation period could potentially modify the immunoglobulin isotype formation with high levels of high-affinity IgE.
Yuki Iwasaki, Kokichi Arisawa, Sakurako Katsuura-Kamano, Hirokazu Uemura, Mineko Tsukamoto, Yuka Kadomatsu, Rieko Okada, Asahi Hishida, Keitaro Tanaka, Megumi Hara, Toshiro Takezaki, Keiichi Shimatani, Etsuko Ozaki, Teruhide Koyama, Sadao Suzuki, Hiroko Nakagawa-Senda, Kiyonori Kuriki, Naoko Miyagawa, Aya Kadota, Hiroaki Ikezaki, Norihiro Furusyo, Isao Oze, Hidemi Ito, Haruo Mikami, Yohko Nakamura and Kenji Wakai : Associations of nutrient patterns with the prevalence of metabolic syndrome: Results from the baseline data of the Japan Multi-Institutional Collaborative Cohort Study, Nutrients, Vol.11, No.5, 990, 2019.
(要約)
The association between nutrient patterns and metabolic syndrome (MetS) has not been examined in a Japanese population. A cross-sectional study was performed on 30,108 participants (aged 35-69 years) in the baseline survey of the Japan Multi-Institutional Collaborative Cohort Study. Dietary intake was assessed using a 46-item food frequency questionnaire. MetS was diagnosed according to the Joint Interim Statement Criteria of 2009, using body mass index instead of waist circumference. Factor analysis was applied to energy-adjusted intake of 21 nutrients, and three nutrient patterns were extracted: Factor 1 (fiber, potassium and vitamins pattern); Factor 2 (fats and fat-soluble vitamins pattern); and Factor 3 (saturated fatty acids, calcium and vitamin B pattern). In multiple logistic regression analysis adjusted for sex, age, and other potential confounders, Factor 1 scores were associated with a significantly reduced odds ratio (OR) of MetS and all five components. Factor 2 scores were associated with significantly increased prevalence of MetS, obesity, and high blood pressure. Factor 3 scores were significantly associated with lower OR of MetS, high blood pressure, high serum triglycerides and low HDL cholesterol levels. Analysis of nutrient patterns may be useful to assess the overall quality of diet and its association with MetS.
Hirokazu Uemura, Sakurako Katsuura-Kamano, Yuki Iwasaki, Kokichi Arisawa, Asahi Hishida, Rieko Okada, Takashi Tamura, Yoko Kubo, Hidemi Ito, Isao Oze, Chisato Shimanoe, Yuichiro Nishida, Yasuyuki Nakamura, Naoyuki Takashima, Sadao Suzuki, Hiroko Nakagawa-Senda, Daisaku Nishimoto, Toshiro Takezaki, Haruo Mikami, Yohko Nakamura, Norihiro Furusyo, Hiroaki Ikezaki, Etsuko Ozaki, Teruhide Koyama, Kiyonori Kuriki, Kaori Endoh, Mariko Naito and Kenji Wakai : Independent relationships of daily life activity and leisure-time exercise with metabolic syndrome and its traits in the general Japanese population., Endocrine, Vol.64, No.3, 552-563, 2019.
(要約)
Our results suggest that higher daily life activity and higher moderate-intensity exercise may be independently associated with a lower risk of metabolic syndrome in Japanese adults.
Gout is a common arthritis caused by elevated serum uric acid (SUA) levels. Here we investigated loci influencing SUA in a genome-wide meta-analysis with 121,745 Japanese subjects. We identified 8948 variants at 36 genomic loci (<5 × 10) including eight novel loci. Of these, missense variants of and were predicted to be damaging to the function of these proteins; another five loci-, , , , and -are related to cell metabolism, proliferation, or oxidative stress; and the remaining locus, , is unknown. We also identified 132 correlated genes whose expression levels are associated with SUA-increasing alleles. These genes are enriched for the UniProt transport term, suggesting the importance of transport-related genes in SUA regulation. Furthermore, trans-ethnic meta-analysis across our own meta-analysis and the Global Urate Genetics Consortium has revealed 15 more novel loci associated with SUA. Our findings provide insight into the pathogenesis, treatment, and prevention of hyperuricemia/gout.
(キーワード)
Alleles / Computational Biology / Genetic Predisposition to Disease / Genome-Wide Association Study / Genotype / Gout / Humans / Japan / Molecular Sequence Annotation / Polymorphism, Single Nucleotide / Quantitative Trait Loci / Quantitative Trait, Heritable / Uric Acid
Basilua Andre Muzembo, Miyuki Iwai-shimada, Tomohiko Isobe, Kokichi Arisawa, Masayuki Shima, Tetsuhito Fukushima and Shoji F. Nakayama : Dioxins levels in human blood after implementation of measures against dioxin exposure in Japan, Environmental Health and Preventive Medicine, Vol.24, No.1, 6, 2019.
(要約)
Over the past few decades, the Japanese Ministry of the Environment has been biomonitoring dioxins in the general Japanese population and, in response to public concerns, has taken measures to reduce dioxin exposure. The objectives of this study were to assess the current dioxin dietary intake and corresponding body burden in the Japanese and compare Japanese dioxin data from 2011 to 2016 and 2002-2010 surveys. We also examined the relationship between blood dioxins and health parameters/clinical biomarkers. From 2011 to 2016, cross-sectional dioxin surveys were conducted on 490 Japanese (242 males and 248 females, aged 49.9 ± 7.6 years) from 15 Japanese prefectures. Blood (n = 490) and food samples (n = 90) were measured for 29 dioxin congeners including polychlorinated dibenzo-para-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and coplanar polychlorinated biphenyls (Co-PCBs) using gas chromatography coupled with high-resolution mass spectrometry. Using the 2006 World Health Organization toxic equivalence factors, the toxic equivalents (TEQs) were calculated. Clinical biomarkers and anthropometric parameters were also measured and information on lifestyle behaviours collected. Data imputations were applied to account for blood dioxins below the detection limit. The median (95% confidence interval or CI) blood levels and dioxin dietary intake was respectively 9.4 (8.8-9.9) pg TEQ/g lipid and 0.3 (0.2-0.4) pg TEQ/kg body weight/day. The median blood dioxin level in the 2011-2016 survey was found to have decreased by 41.3% compared to the 2002-2010 surveys. Participants who were older were found to be more likely to have higher dioxin levels. Blood dioxins were also significantly associated with body mass index, triglycerides, docosahexaenoic acid, eicosapentaenoic acid, and dihomo-gamma-linoleic acid levels in blood. Furthermore, associations between blood dioxin and dietary dioxin intake were evident in the unadjusted models. However, after adjusting for confounders, blood dioxins were not found to be associated with dietary dioxin intake. Blood dioxin levels declined over the past decade. This study showed that the measures and actions undertaken in Japan have possibly contributed to these reductions in the body burden of dioxins in the Japanese population.
Tetsuya Matsuura, Toshiyuki Iwame, Naoto Suzue, Shoichiro Takao, Susumu Nishio, Kokichi Arisawa and Koichi Sairyo : Cumulative Incidence of Osteochondritis Dissecans of the Capitellum in Preadolescent Baseball Players., Arthroscopy : the Journal of Arthroscopic & Related Surgery, Vol.35, No.1, 60-66, 2019.
(要約)
The risk of OCD of the capitellum developing within a 1-year period in preadolescent baseball players was 1.8%. Players aged 10 to 11 years had a significantly greater risk of capitellar OCD development than those aged 6 to 9 years.
M Hara, T Hachiya, Y Sutoh, K Matsuo, Y Nishida, C Shimanoe, K Tanaka, A Shimizu, K Ohnaka, T Kawaguchi, I Oze, F Matsuda, H Ito, S Kawai, A Hishida, R Okada, T Sasakabe, A Hirata, R Ibusuki, Y Nindita, N Furusyo, H Ikezaki, N Kuriyama, E Ozaki, H Mikami, Y Nakamura, S Suzuki, A Hosono, Sakurako Katsuura-Kamano, Kokichi Arisawa, K Kuriki, K Endoh, N Takashima, A Kadota, M Nakatochi, Y Momozawa, M Kubo, M Naito and K Wakai : Genomewide Association Study of Leisure-Time Exercise Behavior in Japanese Adults, Medicine and Science in Sports and Exercise, Vol.50, No.12, 2433-2441, 2018.
(要約)
Although several genetic factors may play a role in leisure-time exercise behavior, there is currently no evidence of a significant genomewide association, and candidate gene replication studies have produced inconsistent results. We conducted a two-stage genomewide association study and candidate single-nucleotide polymorphisms (SNP) association study on leisure-time exercise behavior using 13,980 discovery samples from the Japan Multi-Institutional Collaborative Cohort (J-MICC) study, and 2036 replication samples from the Hospital-based Epidemiologic Research Program at Aichi Cancer Center-2 study. Leisure-time physical activity was measured using a self-administered questionnaire that inquired about the type, frequency and duration of exercise. Participants with ≥4 MET·h·wk of leisure-time physical activity were defined as exhibiting leisure-time exercise behavior. Association testing using mixed linear regression models was performed on the discovery and replication samples, after which the results were combined in a meta-analysis. In addition, we tested six candidate genetic variants derived from previous genomewide association study. We found that one novel SNP (rs10252228) located in the intergenic region between NPSR1 and DPY19L1 was significantly associated with leisure-time exercise behavior in discovery samples. This association was also significant in replication samples (combined P value by meta-analysis = 2.2 × 10). Several SNP linked with rs10252228 were significantly associated with gene expression of DPY19L1 and DP19L2P1 in skeletal muscle, heart, whole blood, and the nervous system. Among the candidate SNP, rs12612420 in DNAPTP6 demonstrated nominal significance in discovery samples but not in replication samples. We identified a novel genetic variant associated with regular leisure-time exercise behavior. Further functional studies are required to validate the role of these variants in exercise behavior.
(キーワード)
Adult / Aged / Cohort Studies / DNA, Intergenic / Exercise / Female / Genome-Wide Association Study / Health Behavior / Humans / Japan / Leisure Activities / Male / Middle Aged / Polymorphism, Single Nucleotide / Surveys and Questionnaires
T Tamura, Y Kadomatsu, M Tsukamoto, R Okada, T Sasakabe, S Kawai, A Hishida, M Hara, K Tanaka, I Shimoshikiryo, T Takezaki, I Watanabe, D Matsui, T Nishiyama, S Suzuki, K Endoh, K Kuriki, Y Kita, Sakurako Katsuura-Kamano, Kokichi Arisawa, H Ikezaki, N Furusyo, YN Koyanagi, I Oze, Y Nakamura, H Mikami, M Naito, K Wakai and Japan Multi-Institutional Collaborative Cohort (J-MICC) Study : Association of exposure level to passive smoking with hypertension among lifetime nonsmokers in Japan: a cross-sectional study, Medicine, Vol.97, No.48, e13241, 2018.
(要約)
Brief exposure to passive smoking immediately elevates blood pressure. However, little is known about the association between exposure to passive smoking and chronic hypertension. We aimed to examine this association in a cross-sectional study, after controlling multiple potential confounders.Participants included 32,098 lifetime nonsmokers (7,216 men and 24,882 women) enrolled in the Japan Multi-Institutional Collaborative Cohort Study. Passive smoking was assessed using a self-administered questionnaire. The single question about exposure to passive smoking had five response options: "sometimes or almost never," "almost every day, 2 hours/day or less," "almost every day, 2 to 4 hours/day," "almost every day, 4 to 6 hours/day," and "almost every day, 6 hours/day or longer." Hypertension was defined as any of the following: systolic blood pressure ≥140 mmHg, diastolic blood pressure ≥90 mmHg, or use of antihypertensive medication. Multivariate-adjusted odds ratio (OR) and 95% confidence interval (CI) for hypertension were estimated by exposure level to passive smoking using unconditional logistic regression models.The multivariate-adjusted OR for hypertension in those exposed almost every day was 1.11 (95% CI: 1.03-1.20) compared with those exposed sometimes or almost never. The OR for a 1-hour per day increase in exposure was 1.03 (95% CI: 1.01-1.06, Pfor trend = .006). This association was stronger in men than in women; the ORs were 1.08 (95% CI: 1.01-1.15, Pfor trend = .036) and 1.03 (95% CI: 1.00-1.05, Pfor trend = .055), respectively.Our findings suggest importance of tobacco smoke control for preventing hypertension.
Hirokazu Uemura, Sakurako Katsuura-Kamano, Mariko Nakamoto, Miwa Yamaguchi, Miho Fujioka, Yuki Iwasaki and Kokichi Arisawa : Inverse association between soy food consumption, especially fermented soy products intake and soy isoflavone, and arterial stiffness in Japanese men., Scientific Reports, Vol.8, No.1, 9667, 2018.
(要約)
Studies on the associations between soy food consumption and arterial stiffness are rare. The aim of the present study was to evaluate their associations in Japanese men. A total of 652 eligible men, aged 35-69 years, who underwent the measurement of brachial-ankle pulse wave velocity (baPWV) as an index of arterial stiffness were evaluated in this cross-sectional study. Information on their lifestyle characteristics, including dietary behavior, was obtained from a structured self-administered questionnaire. The frequency of total soy products as well as fermented and non-fermented soy products intakes was calculated, and the amounts of soy protein and soy isoflavone intakes were also estimated; these were then divided into tertiles and their associations with baPWV values were evaluated using general linear models. Higher frequency of fermented soy products intake was associated with decreased baPWV after adjusting for the multivariable covariates (P value for trend was 0.002, in Model 3). This association did not alter after further adjustment with a biomarker of systemic inflammation (serum high-sensitivity C-reactive protein (hs-CRP)) (P value for trend was 0.001, in Model 4). Total soy isoflavone consumption was also inversely associated with baPWV even after adjusting for multivariable covariates including serum hs-CRP (P value for trend was 0.043, in Model 4); however total soy protein consumption was not. These results demonstrated that greater consumption of soy food, especially fermented soy products and soy isoflavone was associated with reduced arterial stiffness, independent of systemic inflammation, in Japanese men.
Kokichi Arisawa : Recent decreasing trends of exposure to PCDDs/PCDFs/dioxin-like PCBs in general populations, and associations with diabetes, metabolic syndrome, and gout/hyperuricemia, The Journal of Medical Investigation : JMI, Vol.65, No.3.4, 151-161, 2018.
(要約)
The author reviewed recent reports about the blood levels and dietary intake of polychlorinated dibenzo-p-dioxins (PCDDs)/furans (PCDFs)/dioxin-like polychlorinated biphenyls (DL-PCBs) to investigate the trends of dioxin exposure, and epidemiologic studies on the associations of blood levels of dioxins with metabolic diseases. In recent years, dietary intake of dioxins has been decreasing, and the means are equal to or less than 1.0 pg Toxic Equivalents (TEQ)/kg/day in the general populations of several countries. The blood levels of dioxins are also decreasing, probably because of reduced dietary intake. Many cross-sectional studies reported positive associations between blood levels of some isomers or TEQ-based concentrations of PCDDs/PCDFs/DL-PCBs and diabetes in general populations. Three cohort studies on populations with heavy exposure and two nested case-control studies on general populations have also been published, but the results are inconsistent. Three large-scale cross-sectional studies and two cohort studies reported an association between blood levels of some isomers or TEQ-based concentrations of PCDDs/PCDFs/DL-PCBs and metabolic syndrome. In addition, three cross-sectional studies reported significant positive associations with gout/hyperuricemia. Further prospective studies and experimental studies are needed to establish cause-effect relationships, and to clarify the biological mechanisms for the association between background exposure to dioxins and potential health effects. J. Med. Invest. 65:151-161, August, 2018.
Naoko Matsui, Hiroyuki Nodera, D Kuzume, N Iwasa, Y Unai, W Sakai, Y Miyazaki, H Yamazaki, Yusuke Osaki, A Mori, T Furukawa, A Tsukamoto-Miyashiro, Y Shimatani, M Yamasaki, Yuishin Izumi, S Kusunoki, Kokichi Arisawa and Ryuji Kaji : Guillan-Barre syndrome in local area in Japan, 2006-2015: an epidemiological and clinical study of 108 patients, European Journal of Neurology, Vol.25, No.5, 718-724, 2018.
(要約)
Many epidemiological studies of Guillain-Barré syndrome (GBS) and Fisher syndrome (FS) have been conducted in Europe and America. In contrast, epidemiological studies are rare in Asia where the GBS subtypes differ from those in Western countries. This study was undertaken to clarify the incidence of GBS and FS in a local area in Japan as well as their seasonal trends. Seventy-one GBS and 37 FS patients were recorded from 2006 to 2015 in an area of approximately 1.5 million inhabitants in Japan. The incidence, seasonal trends and clinical features of GBS and FS were examined. The incidence rate of GBS was 0.42 cases per 100 000 person-years and that of FS was 0.22 cases per 100 000 person-years. The incidence of GBS increased with age and FS affected predominantly patients aged from 45 to 64 years old. There was some seasonal clustering of acute motor axonal neuropathy (AMAN) and FS in spring and summer, but it was not significant. AMAN and FS patients had a high frequency of preceding infection (AMAN, 68% gastrointestinal infection; FS, 65% upper respiratory infection). Antecedent respiratory infection was significantly associated with FS as an outcome. Serum antibodies to ganglioside GM1 were detected in 71% of AMAN patients and antibodies to GQ1b were detected in 81% of FS patients. Our study offers evidence of a lower incidence of GBS and a higher incidence of FS in a local area in Japan than in Western countries.
A Hishida, M Nakatochi, M Akiyama, Y Kamatani, T Nishiyama, H Ito, I Oze, Y Nishida, M Hara, N Takashima, TC Turin, M Watanabe, S Suzuki, R Ibusuki, I Shimoshikiryo, Y Nakamura, H Mikami, H Ikezaki, N Furusyo, K Kuriki, K Endoh, T Koyama, D Matsui, Hirokazu Uemura, Kokichi Arisawa, T Sasakabe, R Okada, S Kawai, M Naito, Y Momozawa, M Kubo, K Wakai and Group Multi-Institutional Collaborative Cohort (J-MICC) Study Japan : Genome-wide association study on renal function traits: Results from the Japan Multi-Institutional Collaborative Cohort Study, American Journal of Nephrology, Vol.47, No.5, 305-314, 2018.
(要約)
Chronic kidney disease (CKD) is a rapidly growing, worldwide public health problem. Recent advances in genome-wide-association studies (GWAS) revealed several genetic loci associated with renal function traits worldwide. We investigated the association of genetic factors with the levels of serum creatinine (SCr) and the estimated glomerular filtration rate (eGFR) in Japanese population-based cohorts analyzing the GWAS imputed data with 11,221 subjects and 12,617,569 variants, and replicated the findings with the 148,829 hospital-based Japanese subjects. In the discovery phase, 28 variants within 4 loci (chromosome [chr] 2 with 8 variants including rs3770636 in the LDL receptor related protein 2 gene locus, on chr 5 with 2 variants including rs270184, chr 17 with 15 variants including rs3785837 in the BCAS3 gene locus, and chr 18 with 3 variants including rs74183647 in the nuclear factor of -activated T-cells 1 gene locus) reached the suggestive level of p < 1 × 10-6 in association with eGFR and SCr, and 2 variants on chr 4 (including rs78351985 in the microsomal triglyceride transfer protein gene locus) fulfilled the suggestive level in association with the risk of CKD. In the replication phase, 25 variants within 3 loci (chr 2 with 7 variants, chr 17 with 15 variants and chr 18 with 3 variants) in association with eGFR and SCr, and 2 variants on chr 4 associated with the risk of CKD became nominally statistically significant after Bonferroni correction, among which 15 variants on chr 17 and 3 variants on chr 18 reached genome-wide significance of p < 5 × 10-8 in the combined study meta-analysis. The associations of the loci on chr 2 and 18 with eGFR and SCr as well as that on chr 4 with CKD risk have not been previously reported in the Japanese and East Asian populations. Although the present GWAS of renal function traits included the largest sample of Japanese participants to date, we did not identify novel loci for renal traits. However, we identified the novel associations of the genetic loci on chr 2, 4, and 18 with renal function traits in the Japanese population, suggesting these are transethnic loci. Further investigations of these associations are expected to further validate our findings for the potential establishment of personalized prevention of renal disease in the Japanese and East Asian populations.
C Shimanoe, T Hachiya, M Hara, Y Nishida, K Tanaka, Y Sutoh, A Shimizu, R Hishida, S Kawai, R Okada, T Tamura, K Matsuo, H Ito, E Ozaki, D Matsui, R Ibuseki, I Shimoshikiryo, N Takashima, A Kadota, Kokichi Arisawa, Hirokazu Uemura, S Suzuki, M Watanabe, K Kuriki, K Endoh, H Mikami, Y Nakamura, Y Momoxawa, M Kubo, M Nakatochi, M Naito and K Wakai : A genome-wide association study of coping behaviors suggests FBXO45 is associated with emotional espression, Genes, Brain, and Behavior, e12481, 2018.
Tirani Bahari, Hirokazu Uemura, Sakurako Katsuura-Kamano, Miwa Yamaguchi, Mariko Nakamoto, Keisuke Miki, Masashi Ishizu and Kokichi Arisawa : Nutrient-derived dietary patterns and their association with metabolic syndrome in a Japanese population, Journal of Epidemiology, Vol.28, No.4, 194-201, 2018.
(要約)
Nutrients have been proposed to be related to metabolic syndrome (MetS). The aims of this study were to identify dietary patterns that correlated with several nutrients using reduced rank regression (RRR) and to examine the association between extracted dietary patterns and prevalence of MetS in a Japanese population. The study population comprised 1,092 Japanese men and women (35-69 years old) who had participated in the baseline survey of the Japan Multi-Institutional Collaborative Cohort Study in Tokushima Prefecture. Dietary patterns were derived with RRR using 46 food items as predictors and six established nutrients (potassium, calcium, vitamin D, vitamin C, insoluble dietary fiber, and carotene) as response variables. Associations between extracted dietary patterns and MetS were then examined with logistic regression models. Among the six dietary patterns, dietary pattern 1 (DP1) explained the largest proportion (60.1%) of variance in the six nutrients. Therefore, only DP1 was selected for further analysis. DP1 was characterized by high intake frequency of vegetables, fruits, fish and small fish, natto (fermented soybeans), and deep-fried tofu. After adjustment for potential confounders, significant inverse associations were found between DP1 score and MetS (odds ratio [OR] for each quartile: 1.00, 0.58, 0.60, 0.52; P = 0.02); DP1 and high blood pressure (P = 0.0002); and DP1 and high blood glucose (P = 0.02). A dietary pattern characterized by high intake of vegetables, fruits, fish and small fish, natto, and deep-fried tofu was associated with reduced prevalence of MetS in a Japanese population.
H Nakagawa-Senda, T Hachiya, A Shimizu, S Hosono, I Oze, M Watanabe, K Matsuo, M Ito, M Hara, Y Nishida, K Endoh, K Kuriki, Sakurako Katsuura-Kamano, Kokichi Arisawa, Y Nindita, R Ibusuki, S Suzuki, A Hosono, H Mikami, Y Nakamura, N Takashima, Y Nakamura, N Kuriyama, E Ozaki, N Furusyo, H Ikezaki, N Nakatochi, N Sasakabe, S Kawai, R Okada, A Hishida, M Naito, K Wakai, Y Momozawa, M Kubo and K Tanaka : A genome-wide association study in the Japanese population idetifies the 12q24 locus for habitual coffee consumption: the J-MICC Study, Scientific Reports, Vol.8, No.1, 1493, 2018.
(要約)
Coffee is one of the most widely consumed beverages worldwide, and its role in human health has received much attention. Although genome-wide association studies (GWASs) have investigated genetic variants associated with coffee consumption in European populations, no such study has yet been conducted in an Asian population. Here, we conducted a GWAS to identify common genetic variations that affected coffee consumption in a Japanese population of 11,261 participants recruited as a part of the Japan Multi-Institutional Collaborative Cohort (J-MICC) study. Coffee consumption was collected using a self-administered questionnaire, and converted from categories to cups/day. In the discovery stage (n = 6,312), we found 2 independent loci (12q24.12-13 and 5q33.3) that met suggestive significance (P < 1 × 10). In the replication stage (n = 4,949), the lead variant for the 12q24.12-13 locus (rs2074356) was significantly associated with habitual coffee consumption (P = 2.2 × 10), whereas the lead variant for the 5q33.3 locus (rs1957553) was not (P = 0.53). A meta-analysis of the discovery and replication populations, and the combined analysis using all subjects, revealed that rs2074356 achieved genome-wide significance (P = 2.2 × 10 for a meta-analysis). These findings indicate that the 12q24.12-13 locus is associated with coffee consumption among a Japanese population.
Sakurako Katsuura-Kamano, Hirokazu Uemura, Miwa Yamaguchi, Mariko Nakamoto, Tirani Bahari, Keisuke Miki, Masashi Ishizu, Fusakazu Sawachika and Kokichi Arisawa : Dietary calcium intake is associated with serum high-sensitivity C-reactive protein level in the general Japanese population, Journal of Clinical Biochemistry and Nutrition, Vol.62, No.1, 89-93, 2018.
(要約)
The beneficial effects of dietary calcium intake on high-sensitivity C-reactive protein levels, a risk factor of cardiovascular disease, have not been fully elucidated. This study investigated the associations between dietary calcium intake and serum high-sensitivity C-reactive protein levels in the general Japanese population. We analyzed the data of 2,019 subjects (1,194 men and 825 women) aged 35 to 69 years in a cross-sectional study of the Japan Multi-Institutional Collaborative Cohort Study. Nutrients intake including calcium were estimated using a validated food-frequency questionnaire. Analysis using a general linear model revealed that dietary calcium intake was inversely associated with serum high-sensitivity C-reactive protein levels ( for trend <0.001) after adjustment for age, sex, research group, leisure-time physical activity, smoking habit, drinking habit, dietary intakes (energy, dietary fiber, saturated fatty acids and vitamin D) and menopausal status. The association was slightly attenuated after additional adjustment for body mass index; however, remained significant ( for trend = 0.008). There were no significant interactions between dietary calcium intakes and sex, body mass index, or vitamin D intake for high-sensitivity C-reactive protein levels. This study have demonstrated that dietary calcium intake was inversely associated with serum high-sensitivity C-reactive protein levels in the general population.
Xiaolin Yang, Mariko Nakamoto, Emi Shuto, Akiko Hata, Nanako Aki, Yosuke Shikama, Yukiko Bandou, Takako Ichihara, Takako Minagawa, Yumi Kuwamura, Ayako Tamura, Hirokazu Uemura, Kokichi Arisawa, Makoto Funaki and Tohru Sakai : Associations between intake of dietary fermented soy food and concentrations of inflammatory markers: a cross-sectional study in Japanese workers, The Journal of Medical Investigation : JMI, Vol.65, No.1-2, 74-80, 2018.
(要約)
Epidemiological investigations have shown that consumption of soybeans or soy foods reduces the risk of the development of cardiovascular disease, cancer and osteoporosis. The aim of this study was to determine the associations between different soy foods and inflammatory markers, including high-sensitivity C-reactive protein (hs-CRP), interleukin (IL)-6, and IL-18, in Japanese workers. The cross-sectional study included 1,426 Japanese workers (1,053 men and 373 women) aged 20 to 64 years. Intake of 12 soy foods was estimated by a validated food frequency questionnaire. Associations of total soy foods, fermented soy food, non-fermented soy food, soy isoflavone with hs-CRP, IL-6, and IL-18 levels were examined by general linear model regression analysis. We found that total fermented soy food intake was inversely associated with multivariable-adjusted geometric concentration of IL-6 in men (Q1:1.03 pg/mL, Q5:0.94 pg /mL;P for trend = 0.031). Furthermore, it was shown that IL-6 concentrations were inversely associated with miso intake (β = -0.068;p = 0.034) and soy sauce intake in men (β = -0.074;p = 0.018). This study suggests that intake of total fermented soy food, miso and soy sauce be associated with IL-6 concentrations in Japanese men. J. Med. Invest. 65:74-80, February, 2018.
Hitoshi Ikushima, Wakatsuki Masaru, Ariga Takuro, Kaneyasu Yuko, Tokumaru Sunao, Isohashi Fumiaki, Ii Noriko, Uno Takashi, Ohno Yatsuya, Kokichi Arisawa and Toita Takafumi : Radiotherapy for vaginal cancer: a multi-institutional survey study of the Japanese Radiation Oncology Study Group, International Journal of Clinical Oncology, 1-7, 2017.
(要約)
Our aim was to assess the patterns of practice and treatment outcomes of definitive radiotherapy (RT) for vaginal cancer in Japan. RT methods and outcomes of patients with vaginal cancer treated with definitive RT or chemoradiotherapy at 10 institutes of the Japanese Radiation Oncology Study Group between January 2000 and March 2010 were retrospectively evaluated. A total of 90 patients were enrolled in the study. The clinical stages were I, II, III, and IVA in 34, 36, 16, and 4 patients, respectively. Seventy patients were treated with three-dimensional conformal RT (3DCRT) and brachytherapy (BT), 12 with BT alone, and 8 with 3DCRT alone. Chemotherapy was administered to 29 patients. The 5-year overall survival and local control rates were 77 and 83% with a median follow-up period of 94 months for surviving or lost patients. The 5-year overall survival rates according to stage were 94, 71, 56, and 75% for stages I, II, III, and IVA, respectively. The 5-year local control rates according to stage were 94, 77, 74, and 75% for stages I, II, III, and IVA, respectively. Twenty-nine percent (6 of 21 patients) of local recurrences occurred between 5 and 10 years after RT. The 10-year local control rate of all patients was 71%. Significant prognostic factors for overall survival by univariate and multi-variate analyses were performance status, tumor size, and pelvic lymph node metastasis. Grade 3 late radiation morbidity of the rectum, pelvic bone, urinary bladder, and skin developed in 9% (8 of 90 patients). Good outcomes similar to those of cervical cancer can be achieved with definitive RT delivered by 3DCRT and/or BT for vaginal cancer. Long follow-up is necessary for a continuing risk of local recurrence after 5 years.
Tirani Bahari, Hirokazu Uemura, Sakurako Katsuura-Kamano, Miwa Yamaguchi, Mariko Nakamoto, Keisuke Miki, Fusakazu Sawachika and Kokichi Arisawa : Association between Dietary Patterns and Serum Adiponectin: A Cross-Sectional Study in a Japanese Population, International Journal of Food Sciences and Nutrition, 1-10, 2017.
(要約)
The aim of this study was to evaluate the associations between dietary pattern, adiponectin and insulin resistance. The study population consisted of 612 men and women aged 35-69 years old who had participated in the baseline survey of Japan Multi-Institutional Collaborative Cohort (J-MICC) Study in Tokushima Prefecture. Diets and lifestyle related variables were assessed by questionnaires. Multiple regression analyses were used to analyse the relations between dietary patterns and high molecular weight (HMW) adiponectin. For further analysis, path analysis was used to test the hypothesised model of association between dietary pattern, serum adiponectin and insulin resistance. The result showed that higher score of bread and dairy pattern was directly associated with increased serum level of adiponectin in women, which was inversely related to homeostasis model assessment of insulin resistance (HOMA-IR). In conclusion, higher consumption of bread and dairy products, and low intake of rice may be associated with increased serum adiponectin in women.
Hirokazu Uemura, Sakurako Katsuura-Kamano, Miwa Yamaguchi, Tirani Bahari, Masashi Ishizu, Miho Fujioka and Kokichi Arisawa : Relationships of serum high-sensitivity C-reactive protein and body size with insulin resistance in a Japanese cohort., PLoS ONE, Vol.12, No.6, e0178672, 2017.
(要約)
Impacts of chronic systemic inflammation and body size and their interaction effect on insulin resistance in Asian populations, in whom obesity is less common, are not fully understood. This study evaluated combined relationships of systemic inflammation and body size with insulin resistance in a Japanese cohort. We analyzed cross-sectional data from 1,074 eligible subjects (536 men and 538 women) aged 35-69 years who participated in the baseline survey of a cohort study in Tokushima Prefecture, Japan. Systemic inflammation level was assessed by serum high-sensitivity C-reactive protein (hs-CRP), and the degree of insulin resistance and beta-cell function were evaluated by the homeostasis model assessment insulin resistance (HOMA-IR) and beta-cell function (HOMA- ), respectively. Overweight and obesity were defined as a body mass index (BMI) of 23.0-24.9 kg/m2 and ·25.0 kg/m2, respectively. Associations between serum hs-CRP (assessed as quartiles and additionally continuous values after log-transformation) and indices of glucose homeostasis were analysed adjusting for probable covariates, including BMI (quartiles). Combined associations of serum hs-CRP ( median, >median) and body size (normal, overweight, obese) with insulin resistance as well as their interaction effect on insulin resistance were also evaluated. Serum hs-CRP was dose-dependently associated with HOMA-IR, but not HOMA- , after adjustment for probable covariates, including BMI. Subjects with obesity and elevated serum hs-CRP (>median) showed a high multivariable-adjusted HOMA-IR value of 1.32 (95% confidence interval (CI) 1.23, 1.41) compared with subjects with normal BMI and low serum hs-CRP ( median) whose multivariable-adjusted HOMA-IR value was 1.14 (95% CI 1.06, 1.21). The interaction effect between body size (normal, overweight, obese) and serum hs-CRP ( median, >median) on HOMA-IR was significant (P for interaction <0.001). Our study suggests that elevated systemic inflammation is dose-dependently associated with increased insulin resistance, independent of the known risk factors, in a Japanese population. Concomitant obesity and elevated systemic inflammation may synergistically contribute to increased insulin resistance.
Tetsuya Matsuura, Toshiyuki Iwame, Naoto Suzue, Kokichi Arisawa and Koichi Sairyo : Risk factors for shoulder and elbow pain in youth baseball players., The Physician and Sportsmedicine, Vol.45, No.2, 140-144, 2017.
(要約)
This study sought to quantify the 1-year cumulative incidence of shoulder and elbow pain among youth baseball players and identify risk factors associated with the occurrence of shoulder and elbow pain. In total, 900 youth baseball players (aged 7-11 years) were enrolled in a 1-year prospective follow-up study. One year later, the players were asked whether they had experienced episodes of shoulder or elbow pain and the following risk factors for such pain were investigated: age, position, length of baseball experience, training hours per week, and history of shoulder or elbow pain. Data for the groups with and without shoulder or elbow pain were analyzed using multivariate logistic regression models. Episodes of shoulder pain were reported by 18.3% of players and episodes of elbow pain were reported by 35.2% of players. Multivariate analysis showed that shoulder pain was associated with pitcher position, catcher position, longer training hours per week, and history of shoulder and elbow pain, and that elbow pain was associated with age, pitcher position, catcher position, longer training hours per week, and history of elbow pain. Length of baseball experience was not associated with shoulder or elbow pain. History of elbow pain, pitcher position, catcher position, and longer training hours per week were associated with both types of pain. History of shoulder pain was associated with shoulder pain but not elbow pain. Age was associated with elbow pain but not shoulder pain.
Tae Sasakabe, Kenji Wakai, Sayo Kawai, Asahi Hishida, Mariko Naito, Sadao Suzuki, Yora Nindita, Kokichi Arisawa, Yoshikuni Kita, Megumi Hara, Nagato Kuriyama, Akie Hirata, Haruo Mikami, Isao Oze, Michiaki Kubo, Hideo Tanaka and Nobuyuki Hamajima : Modification of the associations of alcohol intake with serum low-density lipoprotein cholesterol and triglycerides by ALDH2 and ADH1B polymorphisms in Japanese men, Journal of Epidemiology, Vol.28, No.4, 185-193, 2017.
(要約)
Although beneficial associations have been reported between moderate alcohol intake and the serum lipid profile, it is unclear whether polymorphisms in alcohol-metabolizing enzymes can modify these associations. Here, we assessed the effects of ADH1B His48Arg (rs1229984), ALDH2 Glu504Lys (rs671), and their combination on these associations. Furthermore, we examined if the findings for ALDH2 could be replicated. We categorized 889 male participants in the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study into two groups based on presence or absence of minor allele(s) or four groups based on genotype combinations. We performed regression analyses of serum lipid concentrations on alcohol intake, with multivariable adjustment. The replication study was conducted among 2,562 men in the Shizuoka part of the J-MICC Study. The ALDH2 Glu/Lys or Lys/Lys groups showed significant decreases in serum low-density lipoprotein (LDL) cholesterol with increasing alcohol consumption; the coefficient per intake increase of 10 g/day was -2.49 mg/dL (95% confidence interval [CI], -3.85 to -1.13), and a significant interaction with the polymorphism was confirmed (P for interaction = 0.006). This inverse correlation was more evident among the ADH1B His/His + ALDH2 Glu/Lys or Lys/Lys groups (-3.24 mg/dL, 95% CI, -5.03 to -1.45). Serum triglycerides were positively associated with alcohol consumption in the ADH1B His/His group (P for interaction = 0.020). The stronger association between serum LDL cholesterol and alcohol consumption in the ALDH2 Glu/Lys or Lys/Lys groups was replicated. The ALDH2 Glu504Lys polymorphism can modify the association between alcohol intake and serum LDL cholesterol in Japanese men.
Hirokazu Uemura, AHMAD AMMAR GHAIBEH, Sakurako Katsuura-Kamano, Miwa Yamaguchi, Bahari Tirani, Masashi Ishizu, Hiroki Moriguchi and Kokichi Arisawa : Systemic inflammation and family history in relation to the prevalence of type 2 diabetes based on an alternating decision tree, Scientific Reports, Vol.7, 45502, 2017.
(要約)
To investigate unknown patterns associated with type 2 diabetes in the Japanese population, we first used an alternating decision tree (ADTree) algorithm, a powerful classification algorithm from data mining, for the data from 1,102 subjects aged 35-69 years. On the basis of the investigated patterns, we then evaluated the associations of serum high-sensitivity C-reactive protein (hs-CRP) as a biomarker of systemic inflammation and family history of diabetes (negative, positive or unknown) with the prevalence of type 2 diabetes because their detailed associations have been scarcely reported. Elevated serum hs-CRP levels were proportionally associated with the increased prevalence of type 2 diabetes after adjusting for probable covariates, including body mass index and family history of diabetes (P for trend = 0.016). Stratified analyses revealed that elevated serum hs-CRP levels were proportionally associated with increased prevalence of diabetes in subjects without a family history of diabetes (P for trend = 0.020) but not in those with a family history or with an unknown family history of diabetes. Our study demonstrates that systemic inflammation was proportionally associated with increased prevalence of type 2 diabetes even after adjusting for body mass index, especially in subjects without a family history of diabetes.
Hirokazu Ogino, Masaki Hanibuchi, Souji Kakiuchi, Atsuro Saijo, Toshifumi Tezuka, Yuko Toyoda, Makoto Tobiume, Kenji Otsuka, Satoshi Sakaguchi, Hisatsugu Goto, Kokichi Arisawa and Yasuhiko Nishioka : Analysis of the prognostic factors of extensive disease small-cell lung cancer patients in Tokushima University Hospital, The Journal of Medical Investigation : JMI, Vol.63, No.3 4, 286-293, 2016.
(要約)
Small-cell lung cancer (SCLC) presents aggressive clinical behavior, and its prognosis is still poor. Previously, performance status (PS), or the existence of brain, bone, or liver metastasis were reported to be unfavorable prognostic factors. Given the recent progress of treatment modalities such as radiotherapy techniques and bone modifying agents, the prognostic factors might be different from previous findings. Therefore, we analyzed the prognostic factors of extensive disease SCLC (ED-SCLC) in recent years. ED-SCLC patients treated in Tokushima University Hospital between 2010 and 2016 were analyzed. Log-rank test and the Cox proportional hazards regression model was used in univariate and multivariate analysis, respectively. Totally, 79 patients were analyzed. In the univariate analysis, age, PS, interstitial pneumonia (IP), liver metastasis, pleural dissemination, neutrophil counts, hypoalbuminemia, hypercalcemia and several liver and biliary enzymes were identified as poor prognostic factors. In the multivariate analysis, age, PS, IP, and liver and biliary enzymes were identified. Moreover, the PS in patients with liver metastasis was significantly worsened. In this study, we newly demonstrated that IP was a significant poor prognostic factor of ED-SCLC. Although liver metastasis was not extracted in multivariate analysis, it may have an impact on the prognosis of ED-SCLC. J. Med. Invest. 63: 286-293, August, 2016.
Tetsuya Matsuura, Naoto Suzue, Toshiyuki Iwame, Kokichi Arisawa, Shoji Fukuta and Koichi Sairyo : Epidemiology of shoulder and elbow pain in youth baseball players., The Physician and Sportsmedicine, Vol.44, No.2, 97-100, 2016.
(要約)
In over 1000 baseball players aged 7 to 12 years, 15.9% reported episodes of shoulder pain, while 29.2% reported elbow pain in the throwing arm. The associated risk factors were different for each type of pain. Shoulder pain was associated with increased age while elbow pain was associated with increased age, increased years of baseball experience, and playing catcher.
Fusakazu Sawachika, Hirokazu Uemura, Sakurako Katsuura-Kamano, Miwa Yamaguchi, Tirani Bahari, Keisuke Miki, Satoshi Todo, Masayuki Inoo, Ikuko Onishi, Noriyuki Kurata and Kokichi Arisawa : Changes in foot function, disease activity, and disability after forefoot resection arthroplasty in patients with rheumatoid arthritis, The Journal of Medical Investigation : JMI, Vol.63, No.1,2, 38-44, 2016.
(要約)
The purpose of this study was to investigate the changes in foot function, disease activity, and disability in patients with RA after resection arthroplasty of the forefoot (arthroplasty). Arthroplasty was performed on 11 patients with RA. All study patients underwent clinical assessment to measure disease activity (Disease Activity Score in 28 Joints-C-reactive protein, DAS28-CRP), disability (Health Assessment Questionnaire-Disability Index, HAQ-DI) and foot function (Foot Function Index, FFI) at the following stages: preoperatively and 1, 3, and 12 months after surgery. Following arthroplasty, foot function improved significantly, as assessed by FFI total and subscales (pain, disability, and limitation of activity) (P<0.001, P<0.001, P<0.001, and P=0.002, respectively). Disease activity was significantly improved in relation to DAS28-CRP and its subscales of number of swollen joints and patient global assessment (PtGA) (P=0.033, P=0.008, and P=0.038, respectively). There was no significant difference in disability, as assessed by the HAQ-DI and its subscale, HAQ-walking (P=0.150 and P=0.597, respectively). Foot function improved significantly after arthroplasty, and was maintained at 12 months postoperatively. Additionally, our study showed that disease activity and its subscale PtGA improved after arthroplasty.
(キーワード)
Aged / Arthritis, Rheumatoid / Arthroplasty / C-Reactive Protein / Female / Forefoot, Human / Humans / Male / Middle Aged / Severity of Illness Index
Yoshitoshi Ogura, Shakhinur Islam Mondal, Md Rakibul Islam, Toshihiro Mako, Kokichi Arisawa, Keisuke Katsura, Tadasuke Ooka, Yasuhiro Gotoh, Kazunori Murase, Makoto Ohnishi and Tetsuya Hayashi : The Shigatosin 2 production level in enterohemorrhagic Escherichia coli O157:H7 is correlated with the subtypes of toxin-encoding phage, Scientific Reports, Vol.5, 16663, 2015.
(要約)
Enterohemorrhagic E. coli (EHEC) causes diarrhea and hemorrhagic colitis with life-threatening complications, such as hemolytic uremic syndrome. Their major virulence factor is Shiga toxin (Stx), which is encoded by bacteriophages. Of the two types of Stx, the production of Stx2, particularly that of Stx2a (a subtype of Stx2), is a major risk factor for severe EHEC infections, but the Stx2 production level is highly variable between strains. Here, we define four major and two minor subtypes of Stx2a-encoding phages according to their replication proteins. The subtypes are correlated with Stx2a titers produced by the host O157 strains, suggesting a critical role of the phage subtype in determining the Stx2a production level. We further show that one of the two subclades in the clade 8, a proposed hyper-virulent lineage of O157, carries the Stx2 phage subtype that confers the highest Stx2 production to the host strain. The presence of this subclade may explain the proposed high virulence potential of clade 8. These results provide novel insights into the variation in virulence among O157 strains and highlight the role of phage variation in determining the production level of the virulence factors that phages encode.
Teruhide Koyama, Daisuke Matsui, Nagato Kuriyama, Etsuko Ozaki, Keitaro Tanaka, Isao Oze, Nobuyuki Hamajima, Kenji Wakai, Rieko Okada, Kokichi Arisawa, Haruo Mikami, Keiichi Shimatani, Akie Hirata, Naoyuki Takashima, Sadao Suzuki, Chisato Nagata, Michiaki Kubo and Hideo Tanaka : Genetic variants of SLC17A1 are associated with cholesterol homeostasis and hyperhomocysteinaemia in Japanese men, Scientific Reports, Vol.5, 15888, 2015.
(要約)
Hyperuricaemia is an undisputed and highly predictive biomarker for cardiovascular risk. SLC17A1, expressed in the liver and kidneys, harbours potent candidate single nucleotide polymorphisms that decrease uric acid levels. Therefore, we examined SLC17A1 polymorphisms (rs1165196, rs1179086, and rs3757131), which might suppress cardiovascular risk factors and that are involved in liver functioning, via a large-scale pooled analysis of the Japanese general population in a cross-sectional study. Using data from the Japan Multi-Institutional Collaborative Cohort Study, we identified 1842 participants of both sexes, 35-69-years-old, having the requisite data, and analysed their SLC17A1 genotypes. In men, logistic regression analyses revealed that minor alleles in SLC17A1 polymorphisms (rs1165196 and rs3757131) were associated with a low-/high-density lipoprotein cholesterol ratio >2.0 (rs1165196: odds ratio [OR], 0.703; 95% confidence interval [CI], 0.536-0.922; rs3757131: OR, 0.658; 95% CI, 0.500-0.866), and with homocysteine levels of >10.0 nmol/mL (rs1165196: OR, 0.544; 95% CI, 0.374-0.792; rs3757131: OR, 0.509; 95% CI, 0.347-0.746). Therefore, these polymorphisms had dominant negative effects on cholesterol homeostasis and hyperhomocysteinaemia, in men, independent of alcohol consumption, physical activity, or daily energy and nutrition intake. Thus, genetic variants of SLC17A1 are potential biomarkers for altered cholesterol homeostasis and hyperhomocysteinaemia in Japanese men.
Miwa Yamaguchi, Hirokazu Uemura, Kokichi Arisawa, Sakurako Katsuura-Kamano, Nobuyuki Hamajima, Asahi Hishida, Shino Suma, Isao Oze, Kazuyo Nakamura, Naoyuki Takashima, Sadao Suzuki, Rie Ibusuki, Haruo Mikami, Keizo Ohnaka, Nagato Kuriyama, Michiaki Kubo and Hideo Tanaka : Association between brain-muscle-ARNT-like protein-2 (BMAL2) gene polymorphism and type 2 diabetes mellitus in obese Japanese individuals: A cross-sectional analysis of the Japan Multi-Institutional Collaborative Cohort Study, Diabetes Research and Clinical Practice, 2015.
(要約)
Brain-muscle-Arnt-like protein-1 (BMAL1) and BMAL2 genes are essential components of the circadian clock, and are considered to be involved in glucose homeostasis. We examined whether single nucleotide polymorphisms (SNPs) of BMAL1 and BMAL2 were associated with the prevalence of type 2 diabetes (T2DM) in the general Japanese population. We studied 2467 subjects (1232 men and 1235 women, 35-69 years old), including 105 men and 57 women with T2DM, from the participants of the Japan Multi-institutional Collaborative Cohort Study. The association between SNPs in the BMAL1 (rs11022775 and rs2290035) and BMAL2 (rs7958822) genes and T2DM were analyzed by multiple logistic regression after adjustment for potential confounders. Analysis was also performed after stratification by body mass index (≥25kg/m(2) and <25kg/m(2)) to investigate an interaction between genotypes and obesity. The A/G and A/A genotypes of BMAL2 rs7958822 showed significantly higher adjusted odds ratios (OR) for T2DM than the G/G genotype among obese men (OR=2.2, 95% confidence intervals [CI] 1.1, 4.6, P for interaction=0.0495) and obese women (OR=2.7, 95% CI 1.1, 6.7, P for interaction=0.199). There were no significant associations between BMAL1 rs11022775 or rs2290035 genotypes and T2DM. To the best of our knowledge, this is the first study to show the significant association between BMAL2 rs7958822 genotype and T2DM among obese subjects.
Hirokazu Uemura, Sakurako Katsuura-Kamano, Miwa Yamaguchi, Kokichi Arisawa, Nobuyuki Hamajima, Asahi Hishida, Sayo Kawai, Isao Oze, Koichi Shinchi, Naoyuki Takashima, Sadao Suzuki, Noriko Nakahata, Haruo Mikami, Keizo Ohnaka, Nagato Kuriyama, Michiaki Kubo and Hideo Tanaka : A variant of the CLOCK gene and related haplotypes are associated with the prevalence of type 2 diabetes in the Japanese population., Journal of Diabetes, Vol.8, No.5, 667-676, 2015.
(要約)
Circadian rhythm disruption is recognized as the cause of various health disorders. This study evaluated associations between single nucleotide polymorphisms in the core circadian gene, CLOCK, and prevalent type 2 diabetes in the Japanese population. We analyzed cross-sectional data from 2,485 subjects (1,243 men and 1,242 women; age, 35-69 years) who were enrolled in the baseline surveys of the Japan Multi-institutional Collaborative Cohort (J-MICC) Study. Associations between 3 CLOCK gene polymorphisms (rs1801260, rs3736544, and rs4864548) and prevalent obesity (BMI ≥25 kg/m(2) ), overweight (BMI ≥23 kg/m(2) ), and diabetes were evaluated by logistic regression analyses; haplotype analysis and stratified analyses for prevalent diabetes were also conducted. Compared to those who were homozygous for the respective major alleles, subjects with the rs1801260 minor allele C showed a significantly higher odds ratio (95% CI) of 1.5 (1.1-2.1) for prevalent diabetes, after adjustment for potential confounding factors, including BMI. When stratified by overweight, the associations between rs1801260 and prevalent diabetes were marked and significant in non-overweight subjects but were not significant in overweight subjects. The TGA (rs1801260 - rs3736544 - rs4864548) haplotype was associated with lower prevalence of diabetes, and the CGG haplotype was associated with higher prevalence of diabetes. CLOCK gene variants and related haplotypes are associated with prevalent type 2 diabetes in the Japanese population in whom obesity is less common, and the association between a CLOCK gene variants at rs1801260 and prevalent diabetes is enhanced in normal-build subjects.
Mariko Nakamoto, Hirokazu Uemura, Tohru Sakai, Sakurako Katsuura-Kamano, Miwa Yamaguchi, Mineyoshi Hiyoshi and Kokichi Arisawa : Inverse association between soy food consumption and insulin resistance in Japanese adults, Public Health Nutrition, Vol.18, No.11, 2031-2040, 2015.
(要約)
The purpose of the present study was to examine the association between soya food consumption and insulin resistance using baseline data of the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study in Tokushima, Japan. This cross-sectional study included 1274 subjects, aged 34-70 years at baseline, living in Tokushima Prefecture between 2008 and 2013. Fasting blood samples were collected and information on lifestyle characteristics including soya food intake and medical history were obtained using a structured self-administered questionnaire. The homeostasis model assessment of insulin resistance (HOMA-IR) was measured and those with HOMA-IR ≥ 2.5 were defined as having insulin resistance. Multiple logistic regression models were used to analyse the association between soya product intake and the prevalence of insulin resistance. Rural communities located in Tokushima Prefecture, Japan, between 2008 and 2013. A total of 1148 adults (565 men and 583 women), aged 34-70 years. The frequency of intake of miso soup, total non-fried soya products and total soya products showed significant inverse dose-response relationships with insulin resistance, after adjustments for potential confounders. When soya product intake was calculated as soya protein and isoflavone, the odds ratios of insulin resistance decreased significantly as the estimated intake of soya protein increased. Furthermore, significant inverse dose-response relationships were observed for total non-fried soya products and total soya products, after adjustment for total vegetable or total fibre consumption. The present results indicate that the intake of soya products and non-fried soya products is associated with reduced insulin resistance in the Japanese population.
Y Sugimoto, K Wakai, H Nakagawa, S Suma, T Sasakabe, T Sakamoto, N Takashima, S Suzuki, S Ogawa, K Ohnaka, N Kuriyama, Kokichi Arisawa, H Mikami, M Kubo, S Hosono, N Hamajima, H Tanaka and Group Study J-MICC : Associations between polymorphisms of interleukin-6 and related cytokine genes and serum liver damage markers: a cross-sectional study in the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study, Gene, Vol.557, No.2, 158-162, 2015.
(要約)
Cytokines, including interleukin-6 (IL-6), play an important role in the liver. The aim of this study was to investigate associations between common polymorphisms in potential functional promoters of cytokine genes and liver damage markers among enrollees of a large Japanese cohort study. Subjects included 3257 Japanese individuals (1608 men and 1649 women, aged 35-69 years). Six single nucleotide polymorphisms (SNPs) in the promoter regions of five cytokine genes, IL1B (T-31C), IL6 (C-634G), IL8 (T-251A), IL10 (T-819C), tumor necrosis factor-A (TNFA) (T-1031C), and TNFA (C-857T), were genotyped by polymerase chain reaction. Information regarding alcohol intake, smoking habits, height, and weight was collected by a self-administered questionnaire. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were measured during a routine health check-up. Of the six SNPs genotyped, an IL6 polymorphism (rs1800796, C-634G) was most strongly associated with a liver damage marker, AST. Mean serum AST was significantly different among the three genotypes (mean ± SD, 22.7 ± 7.3 IU/L for CC, 22.8 ± 7.7 IU/L for CG, and 24.3 ± 8.6 IU/L for GG, p=0.011 by analysis of variance). The differences remained significant after adjustment for potential confounders by general linear models. The variations in mean serum AST and ALT levels were marked especially among men. Thus, the functional polymorphism IL6 C-634G may affect serum AST and ALT levels, possibly through different IL-6 production.
Hirokazu Uemura, Sakurako Katsuura-Kamano, Miwa Yamaguchi and Kokichi Arisawa : Relationships of elevated levels of serum hepatic enzymes and alcohol intake with arterial stiffness in men., Atherosclerosis, Vol.238, No.1, 83-88, 2014.
(要約)
The present study aimed to evaluate the relationships between elevated serum levels of hepatic enzymes and arterial stiffness and to investigate whether alcohol intake had a modifying effect on these relationships in Japanese men. A total of 647 eligible men aged 35-69 years who underwent measurement of brachial-ankle pulse wave velocity (baPWV) as an index of arterial stiffness were evaluated. Information on their lifestyle characteristics were obtained from a structured self-administered questionnaire. Serum biochemical factors, including alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT), were determined. The serum ALT and GGT levels were divided into tertiles, and their associations with baPWV values were evaluated using general linear models adjusted for potential confounding factors. The interaction effects between serum hepatic enzymes and alcohol intake on baPWV were further evaluated. Elevated serum ALT and GGT levels were proportionally associated with increased baPWV after adjusting for the multivariable covariates (P values for trend, 0.004 and 0.003, respectively). Further analyses revealed that the proportional associations between serum levels of hepatic enzymes and baPWV were striking in the subjects without alcohol intake but not in those with alcohol intake. The interaction effect between serum GGT level and alcohol intake on baPWV was significant (P for interaction, 0.042). These results demonstrate that elevated serum ALT and GGT levels are associated with increased arterial stiffness, independent of the classical atherosclerotic risk factors in Japanese men, and that the association of elevated serum GGT level with arterial stiffness differs according to alcohol intake.
Hirokazu Uemura, Sakurako Katsuura-Kamano, Miwa Yamaguchi, Mariko Nakamoto, Mineyoshi Hiyoshi and Kokichi Arisawa : Family history of stroke is potentially associated with arterial stiffness in the Japanese population., Archives of Cardiovascular Diseases, Vol.107, No.12, 654-663, 2014.
(要約)
Studies on the association between family history of cardiovascular disease and arterial stiffness are rare. This study evaluated the possible relationship between family history of cardiovascular disease and arterial stiffness in the Japanese population, by measuring brachial-ankle pulse wave velocity (ba-PWV). A total of 1004 eligible subjects (664 men and 340 women) aged 35-69 years, who were enrolled in the baseline survey of a cohort study in Tokushima Prefecture (Japan) and who underwent ba-PWV measurement, were analysed. Information about their lifestyle characteristics and first-degree family histories of ischaemic heart disease (i.e. myocardial infarction or angina pectoris), stroke or hypertension were obtained from a structural self-administered questionnaire. Subjects of both sexes with a family history of stroke showed significantly higher multivariable-adjusted means of ba-PWV than those without that trait (P values were 0.001 in men and 0.002 in women), while those with a family history of ischaemic heart disease did not. Subjects of both sexes with a family history of hypertension showed significantly higher age-adjusted means of ba-PWV than those without that trait, although these differences disappeared after further adjusting for blood pressure or multivariable covariates. When family histories of these diseases were inserted simultaneously into the same model, these results did not alter substantially. A family history of stroke might be associated with increased arterial stiffness, independent of other known atherosclerotic risk factors, including hypertensive elements, in both sexes in the Japanese population.
Hirokazu Uemura, Sakurako Katsuura-Kamano, Miwa Yamaguchi, Mariko Nakamoto, Mineyoshi Hiyoshi and Kokichi Arisawa : Association between dietary calcium intake and arterial stiffness according to dietary vitamin D intake in men., British Journal of Nutrition, Vol.112, No.8, 1333-1340, 2014.
(要約)
Studies on the associations of dietary Ca and vitamin D intakes with arterial stiffness are scarce. In the present study, these associations were evaluated in Japanese men. Data from a total of 535 eligible men, aged 35-69 years, who participated in the baseline survey of a cohort study in Tokushima Prefecture, Japan, and underwent brachial-ankle pulse wave velocity (ba-PWV) measurements were analysed. ba-PWV is a measure of arterial stiffness and is recognised as a marker of atherosclerotic vascular damage. Information regarding the cohort's lifestyle characteristics including dietary behaviour over the past year was obtained from a structured self-administered questionnaire. Dietary Ca and vitamin D intakes were adjusted for total energy intake using the residual method and divided into quartiles; the highest quartile was used as the reference. General linear models were used to evaluate the associations between dietary Ca and vitamin D intakes and ba-PWV values adjusted for probable covariates. The association between dietary Ca intake and ba-PWV was further evaluated using similar general linear models stratified by dietary vitamin D intake (median or below/above median). Dietary Ca intake was found to be significantly inversely associated with ba-PWV after adjusting for probable covariates (P for trend = 0·020). However, no such association was observed between dietary vitamin D intake and ba-PWV. The inverse association between dietary Ca intake and ba-PWV was striking in subjects with higher dietary vitamin D intake. However, no association was found in subjects with lower dietary vitamin D intake. These results indicate that adequate dietary Ca and vitamin D intakes may be protective against the development of arterial stiffness in Japanese men.
(キーワード)
Adult / Aged / Ankle Brachial Index / Atherosclerosis / Biological Markers / Calcium / Calcium, Dietary / Cohort Studies / Cross-Sectional Studies / Diet / Health Surveys / Humans / Japan / Male / Middle Aged / Prospective Studies / Pulse Wave Analysis / Risk Factors / Vascular Stiffness / Vitamin D / Vitamin D Deficiency
Kokichi Arisawa, Hirokazu Uemura, Miwa Yamaguchi, Mariko Nakamoto, Mineyoshi Hiyoshi, Fusakazu Sawachika and Sakurako Katsuura-Kamano : Associations of dietary patterns with metabolic syndrome and insulin resistance: a cross-sectional study in a Japanese population, The Journal of Medical Investigation : JMI, Vol.61, No.3,4, 333-344, 2014.
(要約)
The associations of dietary patterns with metabolic syndrome (MetS) and insulin resistance have not been fully investigated in the Japanese population. A cross-sectional study was performed on 513 subjects without treatment for diabetes who had participated in the baseline survey of a cohort study in Tokushima Prefecture, Japan. Frequencies of consumption of 46 foods and beverages were assessed using a questionnaire. MetS was diagnosed using the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) criteria. Logistic and linear regression analyses were used to examine the associations of the dietary patterns with the prevalence of MetS, its components, and the Homeostasis Model of Assessment-Insulin Resistance (HOMA-IR). Using principal component analysis, four dietary patterns were extracted: prudent diet (high intake of vegetables and fruits); high fat/Western (high intake of fried foods, fried dishes and meat); bread and dairy products; and seafood patterns. After adjustment for sex, age, and other potential confounders, prudent diet pattern scores were inversely correlated with the prevalence of reduced serum high-density lipoprotein cholesterol (P=0.04) and high blood pressure (P=0.05), and bread and dairy products pattern scores were correlated with a lower prevalence of abdominal obesity (P=0.04) and high plasma glucose (P=0.04). The high fat/Western pattern was positively correlated with HOMA-IR (P=0.04). Prudent dietary pattern and bread and dairy products pattern may be correlated with a lower prevalence of some components of MetS. A high fat/Western dietary pattern may be positively associated with insulin resistance in the Japanese population.
Sakurako Kamano, Hirokazu Uemura, Kokichi Arisawa, Miwa Yamaguchi, Hamajima Nobuyuki, Wakai Kenji, Okada Rieko, Suzuki Sadao, Taguchi Naoto, Kita Yoshikuni, Ohnaka Keizo, Kairupan Sefanya Tara, Matsui Daisuke, Oze Isao, Mikami Haruo, Kubo Michiaki and Tanaka Hideo : A polymorphism near MC4R gene (rs17782313) is associated with serum triglyceride levels in the general Japanese population: the J-MICC Study, Endocrine, Vol.47, No.1, 81-89, 2014.
(要約)
Previously reported associations of a common polymorphism near melanocortin-4 receptor (MC4R) gene (rs17782313) with BMI/obesity were inconsistent, especially in East Asia, and the associations of the polymorphism with serum lipid levels have not been fully elucidated. This study evaluated the association between rs17782313 and obesity-related traits and serum lipid levels in the general Japanese population. A total of 2,035 subjects (aged 35-69 years, 1,024 males and 1,011 females) enrolled in the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study. We examined the associations between near MC4R polymorphism (rs17782313) and obesity-related traits [height, weight, body mass index (BMI), weight change from 20 years old], serum lipid levels (triglycerides, total and HDL-cholesterol), and intake of nutrients (total energy and macronutrients). Polymorphism of rs17782313 (minor C allele) was positively associated with serum triglyceride levels (P for trend = 0.020) adjusted for age and sex. Analysis using a general linear model revealed that the number of minor C alleles was positively associated with serum triglyceride levels after adjustment for age, sex, and potential confounders (P for trend = 0.004). Statistical significance did not change after further adjustment for total energy intake and BMI. There was no significant association between rs17782313 and obesity-related traits including BMI. Interactions between rs17782313 and sex, BMI, or total energy intake for triglyceride levels were not significant. To our knowledge, this study demonstrated for the first time that rs17782313 was associated with serum triglyceride levels in Asian population. Further studies are needed to confirm this result.
(キーワード)
Adult / Aged / Asian Continental Ancestry Group / Body Mass Index / Female / Genetic Association Studies / Genetic Loci / Humans / Japan / Lipid Metabolism / Male / Middle Aged / Multicenter Studies as Topic / Polymorphism, Single Nucleotide / Receptor, Melanocortin, Type 4 / Triglycerides
Hirokazu Uemura, Sakurako Katsuura-Kamano, Miwa Yamaguchi, Fusakazu Sawachika and Kokichi Arisawa : Serum hepatic enzyme activity and alcohol drinking status in relation to the prevalence of metabolic syndrome in the general Japanese population., PLoS ONE, Vol.9, No.4, e95981, 2014.
(要約)
Studies on the combined associations of elevated serum hepatic enzyme activity and alcohol drinking with metabolic syndrome are rare. Our objectives were to evaluate the associations of elevated serum hepatic enzyme activity with the prevalence of metabolic syndrome in the general Japanese population and whether alcohol drinking had a modifying effect on these associations. We conducted a cross-sectional study with 1,027 men and 1,152 women throughout Japan during 2002-2010. Biochemical factors including alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT) were determined in overnight fasting blood, and a survey on lifestyle was conducted by questionnaire. Serum ALT and GGT levels were divided into tertiles in men and women, and their associations with the prevalence of metabolic syndrome were evaluated by logistic regressions. Elevated serum ALT and GGT, even within the reference range, were independently associated with increased metabolic syndrome prevalence and were associated with most of its components in both sexes, except for the association between GGT and low high-density lipoprotein (HDL) cholesterol in men. Stratified analyses by alcohol drinking status revealed that within the same tertile category of serum ALT and GGT, subjects classified as alcohol abstainers showed higher adjusted odds ratios for metabolic syndrome prevalence than those classified as regular alcohol drinkers in both sexes. The interaction effects of serum GGT with alcohol drinking status on metabolic syndrome prevalence were significant in both sexes. These results suggest that elevated serum ALT and GGT, even within the reference range, are independently associated with increased metabolic syndrome prevalence, especially in alcohol abstainers, in Japanese men and women.
Ai Miyashiro, Naoko Matsui, Yoshimitsu Shimatani, Hiroyuki Nodera, Yuishin Izumi, Satoshi Kawabata, Tomihiro Imai, Masayuki Baba, Tetsuo Komori, Masahiro Sonoo, Takahiro Maezaki, Jun Kawamata, Takefumi Hitomi, Nobuo Kohara, Kimiyoshi Arimura, Shuji Hashimoto, Kokichi Arisawa, Susumu Kusunoki and Ryuji Kaji : Are multifocal motor neuropathy patients underdiagnosed? An epidemiological survey in Japan, Muscle & Nerve, Vol.49, No.3, 357-361, 2014.
(要約)
Our objective was to do an epidemiologic survey of patients with multifocal motor neuropathy (MMN) in comparison with those with amyotrophic lateral sclerosis (ALS) in Japan. In this retrospective study, we examined 46 patients with MMN and 1,051 patients with ALS from major neuromuscular centers in Japan from 2005 to 2009. Diagnosis was based on the European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS) and the revised El Escorial criteria. The efficacy of intravenous immunoglobulin (IVIg) was also taken into consideration in the diagnosis of MMN. The ratio of MMN to ALS patients (0-0.10) varied among the centers, but mostly converged to 0.05. The prevalence was estimated to be 0.29 MMN patients and 6.63 ALS patients per 100,000 population. The frequency of MMN patients was around 1 out of 20 ALS patients, and MMN was possibly underdiagnosed in some centers.
(キーワード)
Adolescent / Adult / Aged / Aged, 80 and over / Amyotrophic Lateral Sclerosis / Evoked Potentials, Motor / Female / Hospitals / Humans / 日本 (Japan) / Male / Middle Aged / Peripheral Nervous System Diseases / Retrospective Studies / Young Adult
Sumika Matsui, Toshiyuki Yasui, A Tani, Takeshi Katou, Hirokazu Uemura, Akira Kuwahara, Toshiya Matsuzaki, Kokichi Arisawa and Minoru Irahara : Effect of ultra-low-dose estradiol and dydrogesterone on arterial stiffness in postmenopausal women., Climacteric, Vol.17, No.2, 191-196, 2013.
(要約)
Abstract Background Ultra-low-dose estradiol is known to improve menopausal symptoms and increase bone mineral density. However, the effect of ultra-low-dose estradiol on vascular function has not been clarified. Objectives We examined the effects of ultra-low-dose estradiol on brachial-ankle pulse wave velocity (baPWV) and circulating markers of cardiovascular risk. Patients and methods Twenty-eight postmenopausal women were enrolled in this study. Fourteen women received oral estradiol (0.5 mg) and dydrogesterone (5 mg) every day for 12 months (ultra-low-dose group) as hormone replacement therapy (HRT) and 14 women as a control group did not receive HRT. The baPWV, lipid profiles, homeostasis model assessment of insulin resistance (HOMA-IR) and vascular inflammatory markers were measured. Results The baPWV level significantly decreased in the ultra-low-dose group (p = 0.037), while the baPWV level did not significantly change in the control group. HOMA-IR tended to decrease in the ultra-low-dose group (p = 0.076). Systolic blood pressure and diastolic blood pressure did not change significantly in either group. Conclusion An HRT regimen using oral ultra-low-dose estradiol and dydrogesterone has an effect on arterial stiffness and insulin resistance.
Hirokazu Uemura, Sakurako Katsuura-Kamano, Miwa Yamaguchi, Mariko Nakamoto, Hiyoshi Mineyoshi, Sawachika Fusakazu and Kokichi Arisawa : A family history of diabetes is not associated with arterial stiffness in non-diabetic Japanese population, Open Journal of Epidemiology, Vol.3, No.4, Article-ID:39843,7pages, 2013.
Mariko Nakamoto, Kokichi Arisawa, Hirokazu Uemura, Sakurako Katsuura-Kamano, Hidenobu Takami, Fusakazu Sawachika, Miwa Yamaguchi, Tomoya Juta, Tohru Sakai, Eisaku Toda, Kei Mori, Manabu Hasegawa, Masaharu Tanto, Masayuki Shima, Yoshio Sumiyoshi, Kenji Morinaga, Kazunori Kodama, Takaichiro Suzuki, Masaki Nagai and Hiroshi Satoh : Association between blood levels of PCDDs/PCDFs/dioxin-like PCBs and history of allergic and other diseases in the Japanese population., International Archives of Occupational and Environmental Health, Vol.86, No.8, 849-859, 2013.
(要約)
Previous studies reported that exposure to dioxins was associated with an increased risk of various diseases in general populations. The aim of this study was to examine the association between levels of dioxins in blood and allergic and other diseases. We conducted a cross-sectional study on 1,063 men and 1,201 women (aged 15-76 years), who were living throughout Japan and not occupationally exposed to dioxins, during 2002-2010. In fasting blood samples, polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and dioxin-like PCBs (DL-PCBs) were analyzed by isotope dilution high-resolution gas chromatography/mass spectrometry. We obtained information on life style and self-reported history of diseases using a questionnaire. Blood pressure, blood levels of hemoglobin A1c, and serum lipids were also measured. Multiple logistic regression models were used to analyze the association between dioxin levels in blood and various diseases. Toxic equivalents of PCDDs/PCDFs and total dioxins showed significant inverse dose-response relationships with atopic dermatitis, after adjustments for potential confounders. The highest quartile for total dioxins had an adjusted odds ratio of 0.26 (95 % confidence interval 0.08-0.70) compared to the reference group (first quartile). The odds ratios for hypertension, diabetes mellitus, hyperlipidemia, gout in men, and gynecologic diseases in women significantly increased with increasing toxic equivalents of PCDDs/PCDFs, DL-PCBs, and total dioxins in blood. The present findings suggest that background exposure to dioxins was associated with reduced risk of atopic dermatitis. The results also support the idea that low-level exposure to dioxins is associated with an increased risk of diabetes, hypertension, and hyperlipidemia.
Hirokazu Uemura, Sakurako Katsuura-Kamano, Miwa Yamaguchi, Mariko Nakamoto, M Hiyoshi and Kokichi Arisawa : Abundant daily non-sedentary activity is associated with reduced prevalence of metabolic syndrome and insulin resistance., Journal of Endocrinological Investigation, 2013.
(要約)
Background: Non-exercise activity thermogenesis (NEAT) has recently drawn attention because of its potential to prevent weight gain. Aim: This study evaluated the relationships between the duration of daily non-sedentary activities and the prevalence of metabolic syndrome and insulin resistance in the Japanese population. Material/Subjects and Methods: A total of 518 eligible subjects (380 men and 138 women) who attended the Tokushima Prefectural General Health Checkup Center and participated in the baseline survey of a cohort study conducted in Tokushima Prefecture, Japan were analyzed. Information about lifestyle characteristics including leisure-time exercise and daily non-exercise activities was obtained from a questionnaire. Logistic and multiple linear regression analyses were performed to evaluate the associations between the duration of daily non-exercise non-sedentary activities (beyond sitting) and prevalence of metabolic syndrome (and its components) and insulin resistance. Results: Subjects with longer duration of daily non-sedentary activities had significantly lower adjusted odds ratios for metabolic syndrome (P for trend = 0.024), abdominal obesity (P for trend = 0.023), and low HDL-cholesterol levels (P for trend = 0.002), after adjustment for sex, age, and other probable covariates including leisure-time exercise. Longer duration of daily non-sedentary activities was further associated with lower Homeostasis Model of Assessment-Insulin Resistance (HOMA-IR) values (P for trend = 0.009). Conclusions: Our results suggest that abundant daily non-sedentary activity might be associated with a lower prevalence of metabolic syndrome, especially for the components of central obesity and low HDL-cholesterol levels, and with a lower prevalence of insulin resistance, independent of leisure-time exercise.
Hirokazu Uemura, Sakurako Katsuura-Kamano, Miwa Yamaguchi, Mariko Nakamoto, M Hiyoshi and Kokichi Arisawa : Consumption of coffee, not green tea, is inversely associated with arterial stiffness in Japanese men., European Journal of Clinical Nutrition, 2013.
(要約)
Background/Objectives:Studies on the associations between coffee and green tea consumption and arterial stiffness are rare. This study evaluated the possible relationships between coffee and green tea consumption and brachial-ankle pulse wave velocity (ba-PWV) values in Japanese men.Subjects/Methods:In total, 540 eligible men who enrolled in the baseline survey of a cohort study in Tokushima Prefecture, Japan, and who underwent ba-PWV measurement were analyzed. Information about lifestyle characteristics including coffee and green tea intake were obtained from a structural self-administered questionnaire. Multiple linear regression analyses were used to evaluate the associations between coffee and green tea consumption and ba-PWV.Results:Subjects with greater coffee consumption were younger and showed higher proportions of current smoking and alcohol consumption. Subjects with greater green tea consumption were older and showed lower proportions of current smoking and alcohol consumption. Greater coffee consumption was significantly inversely associated with ba-PWV after the adjustment for probable covariates, including serum low-density lipoprotein cholesterol and high-density lipoprotein cholesterol (P for trend =0.031). After additional adjustment for serum triglycerides, this inverse association persisted, but was somewhat attenuated (P for trend =0.050). In contrast, green tea consumption was not associated with ba-PWV.Conclusions:Coffee consumption was inversely associated with arterial stiffness independent of known atherosclerotic risk factors, and this association was partly mediated by reduced circulating triglycerides. Further prospective or interventional studies are needed to confirm the causal association.European Journal of Clinical Nutrition advance online publication, 17 July 2013; doi:10.1038/ejcn.2013.132.
A Hishida, R Okada, M Naito, E Morita, T Wakai, N Hamajima, S Hosono, H Nanri, TC Turin, S Suzuki, K Kuwabara, H Mikami, S Budhathoki, I Watanabe, Kokichi Arisawa, M Kubo and H Tanaka : Polymorphisms in genes encoding antioxidant enzymes (SOD2, CAT, GPx, TXNRD, SEPP1, SEP15 and SELS) and risk of chronic kidney disease in Japanese - cross-sectional data from the J-MICC study, Journal of Clinical Biochemistry and Nutrition, Vol.53, No.1, 15-20, 2013.
(要約)
Chronic kidney disease (CKD) is well known as a strong risk factor for both of end-stage renal disease and cardiovascular disease. To clarify the association of polymorphisms in the genes encoding antioxidant enzymes (SOD2, CAT, GPx, TXNRD, SEPP1, SEP15 and SELS) with the risk of CKD in Japanese, we examined this association using the cross-sectional data of Japan Multi-Institutional Collaborative Cohort (J-MICC) Study. The subjects were 3,285 men and women, aged 35-69 years, selected from J-MICC Study participants for whom genotyping were conducted by multiplex polymerase chain reaction-based Invader assay. The prevalence of CKD was determined for CKD stages 3-5 (eGFR <60 ml/min/1.73 m(2)). When those with CAT C-262T C/C were defined as reference, those with CAT C-262T C/T demonstrated the OR for CKD of 0.67 (95% CI 0.43-1.06) with the marginally significant trend for decreased odds ratio with increasing numbers of T allele (p = 0.070). There were no significant associations between the other polymorphisms with CKD risk. The present study found a marginally significant trend of the decreased risk of CKD with increasing numbers of T allele of CAT, which may suggest the possibility of personalized risk estimation of this life-limiting disease in the near future.
Miwa Yamaguchi, Kokichi Arisawa, Hirokazu Uemura, Sakurako Katsuura-Kamano, Hidenobu Takami, Fusakazu Sawachika, Mariko Nakamoto, Tomoya Juta, Eisaku Toda, Kei Mori, Manabu Hasegawa, Masaharu Tanto, Masayuki Shima, Yoshio Sumiyoshi, Kenji Morinaga, Kazunori Kodama, Takaichiro Suzuki, Masaki Nagai and Hiroshi Satoh : Consumption of seafood, serum liver enzymes, and blood levels of PFOS and PFOA in the Japanese population., Journal of Occupational Health, Vol.55, No.3, 184-194, 2013.
(要約)
Perfluorooctanesulfonate (PFOS) and perfluorooctanoate (PFOA) have been shown to accumulate in the human body. The purpose of the present study was to examine the factors associated with the blood levels of PFOS and PFOA. A cross-sectional study was performed on 307 men and 301 women (aged 16-76 years) living in 15 prefectures in Japan. Blood levels of PFOS and PFOA were measured by liquid chromatography-mass spectrometry. Hepatic enzymes (-GTP, GOT, and GPT) and -3 polyunsaturated fatty acids (DHA and EPA) levels in serum were also measured. Associations between the levels of PFOS and PFOA in blood and the intake frequency of 41 kinds of dishes, foods and beverages and the serum levels of liver enzymes and -3 polyunsaturated fatty acids were examined using rank correlations. Frequency of intake of boiled fish in broth, sliced raw fish and coastal fish showed significant positive correlations with PFOS concentrations in blood after adjustments for potential confounders. Serum levels of GOT, GPT, DHA and EPA showed significant positive correlations with PFOS and PFOA in blood. There was also a significant regional difference in the blood levels of PFOS and 2013PFOA, with medians being highest in the Tokai/Hokuriku/Kinki region. These findings suggest that the concentrations of PFOS in blood were mainly associated with fish consumption and that the levels of PFOS and PFOA were associated with the serum levels of liver enzymes in Japanese populations. Further investigations are required to clarify the reason for the regional differences in blood levels of PFOS and PFOA in Japan.
K Wakai, K Matsuo, F Matsuda, R Yamada, M Takahashi, T Kawaguchi, Y Yatabe, H Ito, S Hosono, K Tajima, M Naito, E Morita, G Yin, T Sakamoto, N Takashima, S Suzuki, N Nakahata, H Mikami, K Ohnaka, Y Watanabe, Kokichi Arisawa, M Kubo, N Hamajima, H Tanaka and Group J-MICC Study the : Genome-wide association study of the genetic factors related to confectionery intake: potential roles of the ADIPOQ gene, Obesity, Vol.21, No.11, 2413-2419, 2013.
(要約)
Objective: The excessive consumption of confectionery might have adverse effects on human health. To screen genetic factors associated with confectionery-intake frequency, a genome-wide association study (GWAS) in Japan was conducted. Design and Methods: For the discovery phase (stage 1), we conducted a GWAS of 939 noncancer patients in a cancer hospital. Additive models were used to test associations between genotypes of approximately 500,000 single-nucleotide polymorphisms (SNPs) and the confectionery-intake score (based on intake frequency). We followed-up association signals with P < 1 × 10(-5) and minor allele frequency >0.01 in stage 1 by genotyping the SNPs of 4,491 participants in a cross-sectional study within a cohort (replication phase [stage 2]). Results: We identified 12 SNPs in stage 1 that were potentially related to confectionery intake. In stage 2, this association was replicated for one SNP (rs822396; P = 0.049 for stage 2 and 4.2 × 10(-5) for stage 1+2) in intron 1 of the ADIPOQ gene, which encodes the adipokine adiponectin. Conclusions: Given the biological plausibility and previous relevant findings, the association of an SNP in the ADIPOQ gene with a preference for confectionery is worthy of follow-up and provides a good working hypothesis for experimental testing.
T Ooka, E Tokuoka, M Furukawa, T Nagamura, Y Ogura, Kokichi Arisawa, S Harada and T Hayashi : Human gastroenteritis outbreak associated with Escherichia albertii, Japan, Emerging Infectious Diseases, Vol.19, No.1, 144-146, 2013.
(要約)
Although Escherichia albertii is an emerging intestinal pathogen, it has been associated only with sporadic human infections. In this study, we determined that a human gastroenteritis outbreak at a restaurant in Japan had E. albertii as the major causative agent.
A Hishida, K Wakai, M Naito, T Tamura, S Kawai, N Hamajima, I Oze, T Imaizumu, T Turin, S Suzuki, M Kheradmand, H Mikami, K Ohnaka, Y Watanabe, Kokichi Arisawa, M Kubo and H Tanaka : Polymorphisms in PPAR genes (PPARD, PPARG and PPARGC1A) and risk of chronic kidney disease in Japanese: cross-sectional data from the J-MICC Study, PPAR Research, Vol.2013, 980471, 2013.
(要約)
Chronic kidney disease (CKD) is well known as a strong risk factor for both end stage renal disease and cardiovascular disease. To clarify the association of polymorphisms in the PPAR genes (PPARD, PPARG, and PPARGC1A) with the risk of CKD in Japanese, we examined this association among the Japanese subjects using the cross-sectional data of J-MICC (Japan Multi-Institutional Collaborative Cohort) Study. The subjects for this analysis were 3,285 men and women, aged 35-69 years, selected from J-MICC Study participants; genotyping was conducted by multiplex polymerase chain reaction-based Invader assay. The prevalence of CKD was determined for CKD stages 3-5 (defined as eGFR < 60 ml/min/1.73 m(2)). Participants with CKD accounted for 17.3% of the study population. When those with PPARD T-842C T/T were defined as reference, those with PPARD T-842C T/C and C/C demonstrated the OR for CKD of 1.26 (95%CI 1.04-1.53) and 1.31 (95%CI 0.83-2.06), respectively. There were no significant associations between the polymorphisms in other PPAR genes and the risk of CKD. The present study found a significantly increased risk of CKD in those with the C allele of PPARD T-842C, which may suggest the possibility of personalized risk estimation of this life-limiting disease in the near future.
Hidenobu Takami, Mariko Nakamoto, Hirokazu Uemura, Sakurako Katsuura, Miwa Yamaguchi, Mineyoshi Hiyoshi, Fusakazu Sawachika, Tomoya Juta and Kokichi Arisawa : Inverse Correlation between Coffee Consumption and Prevalence of Metabolic Syndrome: Baseline Survey of the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study in Tokushima, Japan, Journal of Epidemiology, Vol.23, No.1, 12-20, 2013.
(要約)
It is unclear whether consumption of coffee and green tea is associated with metabolic syndrome. This cross-sectional study enrolled 554 adults who had participated in the baseline survey of the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study in Tokushima Prefecture, Japan. Consumption of coffee and green tea was assessed using a questionnaire. Metabolic syndrome was diagnosed using the criteria of the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) and the Japan Society for the Study of Obesity (JASSO). Logistic regression analysis was used to examine the association between consumption of coffee and green tea and prevalence of metabolic syndrome and its components. After adjustment for sex, age, and other potential confounders, greater coffee consumption was associated with a significantly lower prevalence of metabolic syndrome, as defined by NCEP ATP III criteria (P for trend = 0.03). Participants who drank more coffee had a lower odds ratio (OR) for high serum triglycerides (P for trend = 0.02), but not for increased waist circumference or high blood pressure. Using JASSO criteria, moderate coffee consumption (1.5 to <3 cups/day) was associated with a significantly lower OR for high plasma glucose (OR = 0.51, 95% CI 0.28-0.93). Green tea consumption was not associated with the prevalence of metabolic syndrome or any of its components. Coffee consumption was inversely correlated with metabolic syndrome diagnosed using NCEP ATP III criteria, mainly because it was associated with lower serum triglyceride levels. This association highlights the need for further prospective studies of the causality of these relationships.
Miwa Yamaguchi, Hirokazu Uemura, Sakurako Katsuura-Kamano, Mariko Nakamoto, Mineyoshi Hiyoshi, Hidenobu Takami, Fusakazu Sawachika, Tomoya Juta and Kokichi Arisawa : Relationship of dietary factors and habits with sleep-wake regularity., Asia Pacific Journal of Clinical Nutrition, Vol.22, No.3, 457-465, 2013.
(要約)
The purpose of this study was to evaluate the associations between dietary factors and sleep-wake regularity in the Japanese population. We analyzed 1368 eligible subjects (931 men and 437 women) aged 35-69 years who had participated in the baseline survey of a cohort study in Tokushima Prefecture, Japan. Information on individual lifestyle characteristics, including dietary habits and sleep-wake regularity, was obtained by a selfadministrated questionnaire. Logistic regression analyses were performed to evaluate adjusted associations of the intake energy ratios of macronutrients, as well as intake frequency, and the amount of staple foods with sleepwake regularity. The lowest quartile of protein intake as well as the highest quartile of carbohydrates showed significantly higher multivariable-adjusted odds ratios of 2.1 (95% confidence interval, 1.3-3.3) and 2.1 (1.3-3.5), respectively, for poor sleep-wake regularity compared with the respective second quartile that is thought to be moderate intake. Regarding intake of staple foods, low weekly intake frequency at breakfast (<5 times/week), the lowest intake amount (<1 bowl or slice/roll) at breakfast, and the highest intake amount (>=2 bowls or slices/ rolls) at lunch and dinner exhibited significantly high adjusted odds ratios for poor sleep-wake regularity. Additionally adjusting for sleep duration, these results did not substantially alter. Our results suggested that low intake energy ratio of proteins and high intake energy ratio of carbohydrates, skipping intake of the staple foods at breakfast, and excessive intake amount of the staple foods at lunch and dinner may be associated with poor sleep-wake regularity.
T Higashibata, N Hamajima, M Naito, S Kawai, G Yin, S Suzuki, Y Kita, H Niimura, T Imaizumi, K Ohnaka, Kokichi Arisawa, M Shigeta, H Ito, H Mikami, M Kubo, H Tanaka and K Wakai : eNOS genotype modifies the effect of leisure-time physical activity on serum triglyceride levels in a Japanese population, Lipids in Health and Disease, Vol.11, 150, 2012.
(要約)
Nitric oxide is a key molecule not only in the cardiovascular system, but also in the metabolic-endocrine system. The purpose of this study was to examine possible associations of the NOS3 T-786C polymorphism (rs2070744) with serum lipid levels on the basis of lifestyle factors for tailoring prevention of dyslipidemia. For this cross-sectional study, a total of 2226 subjects aged 35 to 69 years (1084 men and 1142 women) were selected from Japanese participants in the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study. They were recruited in eight areas throughout Japan between February 2004 and November 2008. In a stratified analysis by leisure-time physical activity, the likelihood of hypertriglyceridemia (serum triglyceride levels ≥ 150 mg/dL) among subjects with the C allele was significantly lower than those without it in the active group (OR = 0.43, 95% CI = 0.22-0.84 in the fasting group), but not in the sedentary group. A gene-environment interaction between the T-786C polymorphism and leisure-time physical activity for hypertriglyceridemia was significant (P = 0.007 in the fasting group). Additionally, serum triglyceride levels (mean ± SD) across leisure-time physical activity classes decreased significantly only in the TC + CC genotype group (111 ± 60 mg/dL for sedentary, 95 ± 48 mg/dL for moderately active, 88 ± 44 mg/dL for very active, P for trend = 0.008 in the fasting group), but not in the TT genotype group. Total cholesterol, high-density lipoprotein (HDL) cholesterol, and non-HDL cholesterol levels had no significant association with the polymorphism. This study suggests that the NOS3 T-786C polymorphism modifies the effect of leisure-time physical activity on serum triglyceride levels.
R Okada, S Kawai, M Naito, A Hishida, N Hamajima, K Shinchi, T Turin Chowdhury, S Suzuki, EM Mantjoro, K Toyomura, Kokichi Arisawa, N Kuriyama, S Hosono, H Mikami, M Kubo, H Tanaka, K Wakai and Group Multi-Institutional Collaborative Cohort (J-MICC) Study Japan : Matrix metalloproteinase-9 gene polymorphisms and chronic kidney disease, American Journal of Nephrology, Vol.36, No.5, 444-450, 2012.
(要約)
The aim of this study was to explore the associations between the prevalence of chronic kidney disease (CKD) and polymorphisms in the genes encoding matrix metalloproteinases (MMPs) and tissue inhibitor of matrix metalloproteinases (TIMPs). MMPs degrade extracellular matrix proteins in the glomerulus, and play important roles in kidney disease progression. DNA samples from 3,309 subjects aged 35-69 years were genotyped for 10 potentially functional polymorphisms in MMP and TIMP genes. The prevalence of CKD (estimated glomerular filtration rate <60 ml/min/1.73 m(2)) was compared among the genotypes. The prevalence of CKD decreased significantly with the number of minor alleles in MMP9 C-1562T (odds ratios (ORs) 0.77 for CT and 0.65 for TT compared with CC; p for trend = 0.023) and MMP9 R668Q (ORs, 0.79 for RQ and 0.64 for QQ compared with RR; p for trend = 0.024). The haplotype MMP9 -1562T/279R/668Q showed a reduced risk for CKD compared with the most common -1562C/279R/668R (OR 0.77, p = 0.008), and the genotype combination -1562TT/ 279RR/668QQ showed a halved risk for CKD compared with major allele homozygous -1562CC/279RR/668RR (OR 0.53, p = 0.091). The potentially functional polymorphisms of MMP9 were associated with the prevalence of CKD in a large Japanese population. These genotypes have been reported to increase MMP9 expression, supporting the hypothesis that MMP-9 has a protective role in the progression of kidney diseases.
Hirokazu Uemura, Mineyoshi Hiyoshi, Kokichi Arisawa, Miwa Yamaguchi, Mariko Naito, Sayo Kawai, Nobuyuki Hamajima, Keitaro Matsuo, Naoto Taguchi, Naoyuki Takashima, Sadao Suzuki, Kazuyo Hirasada, Haruo Mikami, Keizo Ohnaka, Aya Yoshikawa, Michiaki Kubo and Hideo Tanaka : Gene variants in PPARD and PPARGC1A are associated with timing of natural menopause in Japanese population, Maturitas, Vol.71, No.4, 369-375, 2012.
(要約)
Timing of menopause affects postmenopausal health risks. The objective of this study was to evaluate the associations of the single nucleotide polymorphisms (SNPs) in peroxisome proliferator-activated receptor (PPAR)-related genes (PPARD, PPARG, and PPARGC1A) and environmental factors with timing of natural menopause among the general Japanese population. We analyzed cross-sectional data from 1758 women aged 40-69 years who were enrolled in the baseline surveys of the Japan Multi-institutional Collaborative Cohort (J-MICC) Study. Associations of timing of natural menopause with its probable covariates and with target gene variants were evaluated by univariate and multivariate Cox proportional hazards models. Lower body mass index and later age at menarche were significantly associated with earlier natural menopause. Women with minor alleles at T-48444C in PPARD showed a significantly higher adjusted hazard ratio of 1.57 (95% confidence interval: 1.18-2.10) for earlier natural menopause. In contrast, women with minor alleles at Thr394Thr in PPARGC1A showed a significantly lower adjusted hazard ratio of 0.86 (0.76-0.97) for earlier natural menopause. These associations did not substantially alter when re-analyzed after excluding the subjects who self-reported a history of diabetes or the subjects whose age was more than 65 years. Gene variants in PPARD and PPARGC1A might be associated with timing of natural menopause, probably through direct actions on the ovaries, among the general Japanese population.
(キーワード)
Adult / Age Factors / Aged / Alleles / Asian Continental Ancestry Group / Body Mass Index / Cross-Sectional Studies / Female / Genotype / Heat-Shock Proteins / Humans / Japan / Menarche / Menopause / Middle Aged / PPAR delta / Polymorphism, Single Nucleotide / Proportional Hazards Models / Transcription Factors
In our previous proteomic study in rat liver damaged by carbon tetrachloride, soluble catechol-O-methyltransferase (COMT) increased as a phosphorylated form and decreased as a dephosphorylated form. This finding raised the possibility that the COMT protein is associated with liver function. Thus, we hypothesized that (1) the COMT gene contributes to liver homeostasis and (2) a COMT polymorphism (rs4680: Val158Met) causing thermolability of enzymatic activity affects liver enzymes (e.g., aspartate aminotransferase (AST), alanine aminotransferase (ALT) and gamma-glutamyl transpeptidase (-GT)) in serum. To investigate (2), we statistically analyzed the association between COMT genotypes and serum ALT activity in a cross-sectional study using data from the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study. We conducted a multiple logistic regression analysis for males (n=838) and females (n=970). Those participants having missing values or a past history of liver cirrhosis or liver cancer were excluded. ALT values were divided into two; elevated (30IU/L ; males n=239, females n=90) and normal (<30IU/L; males n=599, females n=880). In females, non-adjusted and adjusted odds ratios for ALT values in the rs4680 A/A homozygote (n=126) compared with the wild-type G/G homozygote (n=397) were 0.37 (95% CI 0.14-0.96) and 0.34 (95% CI 0.13-0.93), respectively. In males, an analysis of the population aged 35-69 did not reveal any significant difference, but the population aged 45-54 had a significant difference in the non-adjusted and adjusted odds ratio in the G/A heterozygote (n=89) (0.50 (95% CI 0.27-0.92) and 0.35 (95% CI 0.18-0.71)) and in the A/A homozygote (n=22) (0.34 (95% CI 0.11-0.99) and 0.22 (95% CI 0.07-0.72)), compared with the G/G homozygote (n=88). These data suggest that the COMT polymorphism affects serum ALT activity to maintain liver function.
The aim of this study was to explore the associations between common potential functional promoter polymorphisms in pro-/anti-inflammatory cytokine genes and kidney function/chronic kidney disease (CKD) prevalence in a large Japanese population. A total of 3,323 subjects aged 35-69 were genotyped for all 10 single nucleotide polymorphisms (SNPs) in the promoter regions of candidate genes with minor allele frequencies of > 0.100 in Japanese populations. The estimated glomerular filtration rate (eGFR) and CKD prevalence (eGFR < 60 ml/min/1.73 m2) of the subjects were compared among the genotypes. A higher eGFR and lower prevalence of CKD were observed for the homozygous variants of IL4 -33CC (high IL-4 [anti-inflammatory cytokine]-producing genotype) and IL6 -572GG (low IL-6 [pro-inflammatory cytokine]-producing genotype). Subjects with IL4 CC + IL6 GG showed the highest mean eGFR (79.1 ml/min/1.73 m2) and lowest CKD prevalence (0.0%), while subjects carrying IL4 TT + IL6 CC showed the lowest mean eGFR (73.4 ml/min/1.73 m2) and highest CKD prevalence (17.9%). The functional promoter polymorphisms IL4 T-33C (rs2070874) and IL6 C-572G (rs1800796), which are the only SNPs that affect the IL-4 and IL-6 levels in Japanese subjects, were associated with kidney function and CKD prevalence in a large Japanese population.
(キーワード)
Adult / Aged / Asian Continental Ancestry Group / Cross-Sectional Studies / Cytokines / Female / Genotype / Humans / Inflammation / Kidney Failure, Chronic / Male / Middle Aged / Polymorphism, Single Nucleotide / Promoter Regions, Genetic
Atsushi Kitayama, Kokichi Arisawa, Hirokazu Uemura, Mineyoshi Hiyoshi, Hidenobu Takami, Fusakazu Sawachika, Miwa Yamaguchi, Mariko Nakamoto, Manabu Hasegawa, Masaharu Tanto, Masayuki Shima, Yoshio Sumiyoshi, Kenji Morinaga, Kazunori Kodama, Taka-ichiro Suzuki, Masaki Nagai and Hiroshi Satoh : Correlations of fish intake and plasma docosahexaenoic acid levels with each congener of PCDDs/PCDFs/dioxin-like PCBs in blood from the Japanese population, International Archives of Occupational and Environmental Health, Vol.84, No.8, 927-951, 2011.
(要約)
The purpose of the present study was to investigate the factors associated with blood levels of each congener of polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and dioxin-like polychlorinated biphenyls (DL-PCBs) in the Japanese population. A cross-sectional study was performed on 1,656 subjects (755 men and 901 women) aged 15-73 years, who were living in 90 different areas of 30 prefectures in Japan. Blood levels of 29 PCDD, PCDF, and DL-PCB congeners were determined by high-resolution gas chromatography/mass spectrometry. In addition, a questionnaire survey on life style, including dietary habit, was carried out. The median total toxicity equivalent (TEQ) was 17 pgTEQ/g lipid. After adjustment for age, sex, body mass index, smoking habit, and consumption of other food groups, six PCDDs/PCDFs with 4-6 substituted chlorine atoms and 10 DL-PCBs, but not HeptaCDD/F or OctaCDD, showed significant positive correlations with the frequency of intake of fish and shellfish. Furthermore, significant positive relationships were also found between plasma levels of docosahexaenoic acid (DHA), a biomarker of fish intake, and 10 PCDDs/PCDFs with 4-6 chlorine atoms and 10 DL-PCBs. The partial correlation coefficients with plasma DHA were significantly higher for DL-PCBs than for PCDDs/PCDFs, and partial correlation coefficients for PCDDs/PCDFs significantly decreased with increasing number of chlorine atoms (Spearman r = -0.80, P = 0.001). Blood levels of PCDDs/PCDFs with 4-6 chlorine atoms and DL-PCBs were positively associated with fish intake in the Japanese population. These results may be explained by the higher degree of bioaccumulation of these congeners in fish and shellfish in the ecosystem, and the high consumption of fish among the Japanese population.
Aya Fukumoto, Toshiaki Hashimoto, Kenji Mori, Yoshimi Tsuda, Kokichi Arisawa and Shoji Kagami : Head circumference and body growth in autism spectrum disorders., Brain & Development, Vol.33, No.7, 569-575, 2011.
(要約)
Research has shown that there is a relationship between increased head circumference and autism spectrum disorders (ASD). This study examined this relationship during the first year of life in subjects with ASD. We compared 280 children with ASD and 609 controls. In the ASD-male group, increases were observed in head circumference from 3 to 12months, in height from 3 to 9months, and in body weight from 3 to 6 and 12months. On the other hand, in the ASD-female group increases in head circumference, in body height, and in body weight were only observed at 3months. After adjusting for height, weight, and age, only the head circumference in the male ASD group was significantly increased from 6 to 9months after birth, reaching a peak at 6months after birth. No difference was found in the female ASD group. Although body overgrowth in the ASD group also started early after birth, the increase in head circumference was more marked than that in body growth. The values of physical measurements in the first year may be useful, minimally invasive parameters for the early detection of autism in combination with observing the timing of certain behaviors such as smiling, eye contact, crawling, pointing, and joint attention.
(キーワード)
Body Height / Body Weight / Cephalometry / Child Development Disorders, Pervasive / Female / Head / Humans / 小児 (infant) / Infant, Newborn / 日本 (Japan) / Male
Sakurako Katsuura, Yoshiko Kamezaki, Naoko Yamagishi, Yuki Kuwano, Kensei Nishida, Kiyoshi Masuda, Toshihito Tanahashi, Tomoko Kawai, Kokichi Arisawa and Kazuhito Rokutan : Circulating vascular endothelial growth factor is independently and negatively associated with trait anxiety and depressive mood in healthy Japanese university students., International Journal of Psychophysiology, Vol.81, No.1, 38-43, 2011.
(要約)
Anxiety and depressive mood are sometimes accompanied by modulation of neuroendocrine and immune functions. The aim of this study was to identify circulating immune mediators reflecting anxiety and depressive mood in healthy young adults. Anxiety and depressive mood in 209 healthy medical students (125 males and 84 females, aged 20.7±2.7years (mean±SD)) were assessed by the Spielberger state-trait anxiety inventory (STAI) and the Zung self-rating depression scale (Zung-SDS), respectively. Cortisol and chromogranin A (CgA) levels in saliva were measured using enzyme immunoassay kits, and 50 different mediators in sera were measured by a multiplex-suspension array system. The level of statistical significance was set at =0.05. Forty-four mediators were measurable in sera, and each mediator showed substantial individual variations. After determining Pearson correlation coefficients, we selected candidate cytokines whose levels were associated with STAI-state (2 cytokines), STAI-trait (8 cytokines), or SDS scores (8 cytokines). The candidate cytokines plus interleukin (IL)-1, IL-6, tumor necrosis factor-, and macrophage migration inhibitory factor were then subjected to multiple regression analysis adjusted for gender, BMI, and salivary concentrations of cortisol and CgA. Vascular endothelial growth factor (VEGF) was independently and negatively associated with both trait anxiety (p<0.05) and depressive mood (p<0.01). IL-1 showed independently positive association with depressive mood (p<0.05). Interactions between these two cytokines and gender or BMI were not observed. Besides IL-1, circulating VEGF may be a potential biomarker for negative mood states in healthy young adults.
(キーワード)
Adolescent / Anxiety / Body Mass Index / 細胞質分裂 (cytokinesis) / Depressive Disorder / Endothelial Growth Factors / 女性 (female) / Humans / Hydrocortisone / 日本 (Japan) / 男性 (male) / Psychiatric Status Rating Scales / Questionnaires / Regression Analysis / Saliva / Sex Factors / Students / Universities / Vascular Endothelial Growth Factor A / Young Adult
Most diseases are thought to arise from interactions between environmental factors and the host genotype. To detect gene-environment interactions in the development of lifestyle-related diseases, and especially cancer, the Japan Multi-institutional Collaborative Cohort (J-MICC) Study was launched in 2005. We initiated a cross-sectional study to examine associations of genotypes with lifestyle and clinical factors, as assessed by questionnaires and medical examinations. The 4519 subjects were selected from among participants in the J-MICC Study in 10 areas throughout Japan. In total, 108 polymorphisms were chosen and genotyped using the Invader assay. The study group comprised 2124 men and 2395 women with a mean age of 55.8 ± 8.9 years (range, 35-69 years) at baseline. Among the 108 polymorphisms examined, 4 were not polymorphic in our study population. Among the remaining 104 polymorphisms, most variations were common (minor allele frequency ≥0.05 for 96 polymorphisms). The allele frequencies in this population were comparable with those in the HapMap-JPT data set for 45 Japanese from Tokyo. Only 5 of 88 polymorphisms showed allele-frequency differences greater than 0.1. Of the 108 polymorphisms, 32 showed a highly significant difference in minor allele frequency among the study areas (P < 0.001). This comprehensive data collection on lifestyle and clinical factors will be useful for elucidating gene-environment interactions. In addition, it is likely to be an informative reference tool, as free access to genotype data for a large Japanese population is not readily available.
Kokichi Arisawa, Hirokazu Uemura, Mineyoshi Hiyoshi, Atsushi Kitayama, Hidenobu Takami, Fusakazu Sawachika, Yuki Nishioka, Manabu Hasegawa, Masaharu Tanto, Hiroshi Satoh, Masayuki Shima, Yoshio Sumiyoshi, Kenji Morinaga, Kazunori Kodama, Taka-ichiro Suzuki and Masaki Nagai : Dietary patterns and blood levels of PCDDs, PCDFs, and dioxin-like PCBs in 1,656 Japanese individuals, Chemosphere, Vol.82, No.5, 656-662, 2011.
(要約)
The association between dietary patterns and blood dioxin levels has not been fully investigated. The present study population consisted of 755 men and 901 women (aged 15-73years) living in 90 different areas of 30 prefectures of Japan. Dietary habits were assessed by inquiring about the consumption frequency of 28 foods, food groups and beverages. In addition, the blood levels of 29 polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzo-furans (PCDFs), and dioxin-like polychlorinated biphenyl (DL-PCBs) congeners were determined by high-resolution gas chromatography/mass spectrometry. The median total toxicity equivalent (TEQ) in the blood, which was calculated on the basis of the toxicity equivalency factors of WHO (2005), was 16 pg TEQg(-1) lipid. Principal component analysis identified five dietary patterns: Healthy diet (high intake of vegetables and fruits); Meat/High fat intake (high intake of meat, meat products, and eggs); Seafood and Alcohol (high intake of fish, shellfish, and alcoholic beverages); Miscellaneous; and Milk products and Alcohol intake (high intake of milk, Milk products, and alcoholic beverages). After adjusting for sex, age, body mass index, and smoking habits, the Seafood and Alcohol pattern scores were significantly related to higher blood levels of total TEQ and PCDDs/PCDFs/DL-PCBs, and the Milk products and Alcohol pattern scores were correlated with higher blood levels of DL-PCBs. More detailed analysis showed that the intake frequencies for alcoholic beverages and seafood were independently and positively associated with total TEQ and the TEQ of PCDFs and DL-PCBs. The association between alcoholic beverage intake and PCDDs was also significant. Analysis of dietary patterns may be useful for identifying the dietary characteristics of individuals with a high dioxin body burden.
Hirokazu Uemura, Kokichi Arisawa, Mineyoshi Hiyoshi, Satoru Dakeshita, Atsushi Kitayama, Hidenobu Takami, Fusakazu Sawachika, Miwa Yamaguchi and Shuhei Sasai : Congener-specific body burden levels and possible determinants of polybrominated diphenyl ethers among general inhabitants in Japan, Chemosphere, Vol.79, No.7, 706-712, 2010.
(要約)
Our objective was to investigate congener-specific body burden levels and possible determinants of polybrominated diphenyl ethers (PBDEs) in the Japanese human population. We conducted a cross-sectional study on 72 participants aged 15-74 years; subjects were not occupationally exposed to PBDEs or dioxin-like polychlorinated biphenyls (DL-PCBs). Participants lived in two urban areas and two fishing villages. Twenty-seven PBDE congeners, PCB-126, PCB-118, PCB-156, and biochemical factors were determined in fasting blood. A questionnaire survey on life-style was also conducted. More than half of the PBDE values for 14 congeners were below the levels of detection (LODs). The median concentration of total PBDEs was 3.6 ng g(-1) lipid. The most abundant congener was BDE-209 (median concentration, 0.90 ng g(-1) lipid), followed by BDE-153, BDE-207, and BDE-47 in the given order. Most PBDE congeners with < or = 6 bromine atoms had significant positive associations with the concentrations of the three DL-PCBs (suggesting common routes of exposure) and with plasma concentrations of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), biological markers of fish intake. These associations did not change substantially after adjustment for age, sex, and log(body mass index). These positive associations with the concentrations of DL-PCBs or EPA/DHA were not found in analyses of high-brominated PBDE congeners with > or = 8 bromine atoms. Fish consumption may be a major contributor to the accumulation of PBDE congeners with 6 bromine atoms among the general Japanese population. In contrast, the main exposure routes to high-brominated PBDEs in humans are probably not associated with fish consumption.
Osteoporosis is a chronic skeletal condition characterized by impaired bone strength and increased risk of fracture. This disorder causes notable morbidity, deterioration in quality of life (QOL)and mortality in the elderly due to associated with fragility fractures of the spine, hip and wrist. Moreover, the treatment of osteoporotic fractures is also associated with a huge economic cost for society. To avoid the fragility fracture, prevention of osteoporosis and fall down are of great importance. For that purpose, not only pharmacological therapy(mainly by antiresorptive medications) in middle-aged and elderly individuals but also non-pharmacological intervention through lifestyle modification will become important in adolescents and young adults from the early life. Lifestyle modification emphasizing bone health such as adequate calcium, vitamin D and vitamin K nutrition, restriction of caffeine and alcohol consumption, and avoidance of tobacco are essential to the management of osteoporosis risk. Balance and strength training also play important roles in the improvement of bone strength. Most of the risk and preventive factors of osteoporosis are common to those of other lifestylerelated diseases. Therefore, lifestyle modification emphasizing bone health from the early life will contribute to avoid not only fragility fracture but also other lifestyle-related diseases, and will contribute to maintenance or improvement of QOL.
Naoko Matsui, S Nakane, Y Nakagawa, Kazuya Kondo, T Mitsui, T Matsumoto, Kokichi Arisawa and Ryuji Kaji : Increasing incidence of elderly onset patients with myasthenia gravis in a local area of Japan, Journal of Neurology, Neurosurgery, and Psychiatry, Vol.80, No.10, 1168-1171, 2009.
(要約)
As the number of elderly patients with myasthenia gravis (MG) has recently increased in Europe and the USA, a retrospective survey of Japanese MG patients was conducted in a single neurological centre over several decades. The study consisted of 112 consecutive MG patients with onset of the disease from 1971 to 2006 from an area of approximately 0.8 million inhabitants in Japan. Patients were classified into three subgroups according to age at onset: young onset (39 years old), middle aged onset (40-59 years old) and elderly onset (60 years old). The trends in incidence rate and clinical features were examined: disease severity, seropositivity for antiacetylcholine receptor antibody, occurrence of other autoimmune diseases, occurrence of thymoma and therapeutic response. The onset adjusted age specific average annual incidence per 100,000 of the elderly onset MG patients increased 20-fold from 1981-1990 (0.06; 95% CI 0.00 to 0.36) to 2001-2006 (1.30; 95% CI 0.77 to 2.05). Clinical features of the elderly onset MG patients included low antiacetylcholine receptor antibody titres (mean 24.6 nmol/l), less frequent autoimmune overlaps (8.0%) and nearly no complete stable remission with or without thymectomy. The increasing incidence of elderly onset MG in Japanese patients similar to that reported in Caucasians has been confirmed. The clinical features suggest different immunological backgrounds between young onset and elderly onset MG patients, irrespective of the ethnic background.
(キーワード)
Adult / Age Distribution / Age of Onset / Aged / Asian Continental Ancestry Group / Catchment Area (Health) / Cohort Studies / Female / Hospitals, University / Humans / Incidence / 日本 (Japan) / Male / Middle Aged / Myasthenia Gravis / Retrospective Studies / Sex Distribution
Tohru Nakagoe, Toshikazu Matsuo, Shirou Nakamura, Chusei Ryu, Goushi Murakami and Kokichi Arisawa : Risk factors preventing success of a minilaparotomy approach in the resection of colorectal cancer, Digestive Surgery, Vol.26, No.3, 236-242, 2009.
(要約)
A minilaparotomy approach is technically feasible for the resection of colorectal cancer in select patients. The aim of this study was to clarify the risk factors preventing the success of a minilaparotomy in the resection of colorectal cancer. Between April 2005 and August 2008, 141 consecutive patients were enrolled in this prospective study and scheduled to undergo resection of colorectal cancer using a minimal skin incision. The minilaparotomy involved a colorectal resection performed through a skin incision <7 cm in length. Neither a hand-port nor a laparoscope was used. A minilaparotomy was successful in 74 (52.5%) of 141 patients. Multivariate logistic regression analysis revealed that the failure of the minilaparotomy in the remaining 67 (47.5%) was independently related to gender (male), BMI (> or =25.5), tumor location (splenic flexure and rectum), tumor adhesion/invasion on/into adjacent organs and the maximum tumor diameter (> or =7.0 cm). Gender (male), BMI (> or =25.5), tumor location (splenic flexure and rectum) and tumor aggressiveness [tumor adhesion/invasion on/into adjacent organs and maximum tumor diameter (> or =7.0 cm)] were independent risk factors preventing the success of the minilaparotomy approach in the resection of colorectal cancer.
(キーワード)
Adult / Aged / Aged, 80 and over / Colorectal Neoplasms / Epidemiologic Methods / Female / Humans / Japan / Laparotomy / Male / Middle Aged / Postoperative Complications / Preoperative Care / Treatment Outcome
Hirokazu Uemura, Kokichi Arisawa, Mineyoshi Hiyoshi, Atsushi Kitayama, Hidenobu Takami, Fusakazu Sawachika, Satoru Dakeshita, Kentaro Nii, Hiroshi Satoh, Yoshio Sumiyoshi, Kenji Morinaga, Kazunori Kodama, Taka-ichiro Suzuki, Masaki Nagai and Tsuguyoshi Suzuki : Prevalence of metabolic syndrome associated with body burden levels of dioxin and related compounds among Japan's general population., Environmental Health Perspectives, Vol.117, No.4, 568-573, 2009.
(要約)
BACKGROUND: Environmental exposure to some persistent organic pollutants has been reported to be associated with a metabolic syndrome in the U.S. population. OBJECTIVES: We evaluated the associations of body burden levels of dioxins and related compounds with the prevalence of metabolic syndrome among the general population in Japan. METHODS: We conducted a cross-sectional study with 1,374 participants not occupationally exposed to these pollutants, living throughout Japan during 2002-2006. In fasting blood samples, we measured biochemical factors and determined lipid-adjusted concentrations of 10 polychlorinated dibenzo-p-dioxins (PCDDs), 7 polychlorinated dibenzofurans (PCDFs), and 12 dioxin-like poly-chlorinated biphenyls (DL-PCBs) all of which have toxic equivalency factors. We also performed a questionnaire survey. RESULTS: The toxic equivalents (TEQs) of PCDDs, PCDFs, and DL-PCBs and total TEQs had significant adjusted associations with metabolic syndrome, whether or not we excluded diabetic subjects. By analyzing each component of metabolic syndrome separately, the DL-PCB TEQs and total TEQs were associated with all components, and the odds ratios (ORs) in the highest quartile of DL-PCB TEQs in four of the five components were higher than those for PCDDs or PCDFs. We also found congener-specific associations with metabolic syndrome; in particular, the highest quartiles of PCB-126 and PCB-105 had adjusted ORs of 9.1 and 7.3, respectively. CONCLUSIONS: These results suggest that body burden levels of dioxins and related compounds, particularly those of DL-PCBs, are associated with metabolic syndrome. Of the components, high blood pressure, elevated triglycerides, and glucose intolerance were most closely associated with these pollutants.
Satoru Dakeshita, Tomoko Kawai, Hirokazu Uemura, Mineyoshi Hiyoshi, Etsuko Oguma, Hyogo Horiguchi, Fujio Kayama, Keiko Aoshima, Satoshi Shirahama, Kazuhito Rokutan and Kokichi Arisawa : Gene expression signatures in peripheral blood cells from Japanese women exposed to environmental cadmium, Toxicology, Vol.257, No.1,2, 25-32, 2009.
(要約)
The objective of this study was to examine the effects of environmental cadmium (Cd) exposure on the gene expression profile of peripheral blood cells, using an original oligoDNA microarray. The study population consisted of 20 female residents in a Cd-polluted area (Cd-exposed group) and 20 female residents in a non-Cd-polluted area individually matched for age (control group). The mRNA levels in Cd-exposed subjects were compared with those in respective controls, using a microarray containing oligoDNA probes for 1867 genes. Median Cd concentrations in blood (3.55 microg/l) and urine (8.25 microg/g creatinine) from the Cd-exposed group were 2.4- and 1.9-times higher than those of the control group, respectively. Microarray analysis revealed that the Cd-exposed group significantly up-regulated 137 genes and down-regulated 80 genes, compared with the control group. The Ingenuity Pathway Analysis Application (IPA) revealed that differentially expressed genes were likely to modify oxidative stress and mitochondria-dependent apoptosis pathways. Among differentially expressed genes, the expression of five genes was positively correlated with Cd concentrations in blood or urine. Quantitative real-time PCR (RT-PCR) analysis validated the significant up-regulation of CASP9, TNFRSF1B, GPX3, HYOU1, SLC3A2, SLC19A1, SLC35A4 and ITGAL, and down-regulation of BCL2A1 and COX7B. After adjustment for differences in the background characteristics of the two groups, we finally identified seven Cd-responsive genes (CASP9, TNFRSF1B, GPX3, SLC3A2, ITGAL, BCL2A1, and COX7B), all of which constituted a network that controls oxidative stress response by IPA. These seven genes may be marker genes useful for the health risk assessment of chronic low level exposure to Cd.
Mineyoshi Hiyoshi, Hiroaki Konishi, Hirokazu Uemura, Hideki Matsuzaki, Hideo Tsukamoto, Ryusuke Sugimoto, Hideo Takeda, Satoru Dakeshita, Atsushi Kitayama, Hidenobu Takami, Fusakazu Sawachika, Hiroshi Kido and Kokichi Arisawa : D-dopachrome tautomerase is a candidate for key proteins to protect the rat liver damaged by carbon tetrachloride, Toxicology, Vol.255, No.1,2, 6-14, 2009.
(要約)
Carbon tetrachloride (CCl4) is known to induce liver damage. Animal experiments with CCl4 injections have revealed many findings, especially mechanisms of liver damage and liver regeneration. Recently, proteomic approaches have been introduced in various studies to evaluate the quantitative and qualitative changes in the comprehensive proteome level. The aim of this research is to elucidate the key protein for liver damage, liver protection and liver regeneration by using proteomic techniques. 50 % (v/v) CCl4 in corn oil was administered intraperitoneally to adult male rats at a dose of 4ml/kg body weight. Approximately 24h after the injection, the liver was removed and extracted proteins were analyzed with cleavable isotope coded affinity tag (cICAT) reagents, two-dimensional gel electrophoresis (2-DE) and mass spectrometry (MS). A twelvefold increase in D-dopachrome tautomerase (DDT) was indicated. This enzyme has been reported to be involved in the biosynthesis of melanin, an antioxidant. According to the histological analysis, melanin levels were increased in un-damaged hepatocytes of CCl4-treated rats. These results suggest that the increase in DDT is a response to liver damage, accelerates melanin biosynthesis and protects the liver from oxidative stress induced by CCl4.
(キーワード)
Animals / Blotting, Western / Body Weight / COS Cells / Carbon Tetrachloride Poisoning / Cercopithecus aethiops / Cloning, Molecular / DNA, Complementary / Drug-Induced Liver Injury / Genetic Vectors / Intramolecular Oxidoreductases / Liver / Male / Mass Spectrometry / Melanins / Organ Size / Rats / Rats, Wistar / Transfection
Kokichi Arisawa, Hirokazu Uemura, Mineyoshi Hiyoshi, Hiroshi Satoh, Yoshio Sumiyoshi, Kenji Morinaga, Kazunori Kodama, Taka-ichiro Suzuki, Masaki Nagai and Tsuguyoshi Suzuki : Dietary intake of PCDDs/PCDFs and coplanar PCBs among the Japanese population estimated by duplicate portion analysis: a low proportion of adults exceed the tolerable daily intake., Environmental Research, Vol.108, No.2, 252-259, 2008.
(要約)
Dietary intake of dioxins was estimated by duplicate portion analysis of consecutive 3-day food samples among 86 men and 288 women (aged 17-72 years), who were living in 75 different areas of 25 prefectures in Japan. The mean (median) intake of PCDDs+PCDFs, coplanar PCBs (co-PCBs), and total dioxins, expressed on the basis of toxicity equivalents (TEQ), was 0.46 (0.34), 0.59 (0.39), and 1.06 (0.79)pg/kg body weight/day, respectively. Dietary intake was highest in fishing areas, followed by farming and urban areas. In multiple regression analysis, TEQs of PCDDs+PCDFs, co-PCBs, and total dioxins were positively associated with age and intake amount of fish and shellfish, and milk and dairy products, and negatively associated with survey year. There were significant positive correlations between dietary intake and blood levels for TEQs of PCDDs+PCDFs, co-PCBs, and total dioxins (Pearson r=0.35-0.36). The proportion of those whose dietary intake exceeded the tolerable daily intake (TDI), set by the World Health Organization (4pg TEQ/kg/day) and European Union (2pg TEQ/kg/day), was estimated at 2.1% and 10.4%, respectively. However, these proportions were considered to be overestimated because of the effect of day-to-day within-person variation. Therefore, the ratio of within- and between-person variance was estimated by applying random effects one-way analysis of variance to repeated measurements for another group of 35 persons. When the effect of within-person variation of dietary intake was accounted for, the proportion of subjects whose long-term intake exceeded the TDI of WHO and EU decreased to 0.06% and 2.9%, respectively.
Hirokazu Uemura, Kokichi Arisawa, Mineyoshi Hiyoshi, Hiroshi Satoh, Yoshio Sumiyoshi, Kenji Morinaga, Kazunori Kodama, Taka-ichiro Suzuki, Masaki Nagai and Tsuguyoshi Suzuki : Associations of environmental exposure to dioxins with prevalent diabetes among general inhabitants in Japan., Environmental Research, Vol.108, No.1, 63-68, 2008.
(要約)
The aim of this study was to evaluate the associations of environmental exposure to dioxins with diabetes among general inhabitants in Japan. A cross-sectional study was performed on 1374 participants, who were not occupationally exposed to dioxins, aged 15-73 years, living widely in 75 different residential areas of 25 prefectures in Japan through 2002-2006. Seven polychlorinated dibenzo-p-dioxins (PCDDs), 10 polychlorinated dibenzofurans (PCDFs), 12 dioxin-like polychlorinated biphenyls (PCBs), which are assigned a toxic equivalency factor, and biochemical factors were determined in fasting blood. A questionnaire survey on life-style including past history of diseases and treatments was also performed. We examined the associations of the accumulated toxic equivalents (TEQs) of PCDDs+PCDFs, dioxin-like PCBs and total dioxins with prevalent diabetes. Simple and partial correlation analyses revealed that HbA1c correlated with the accumulated TEQs of PCDDs+PCDFs, dioxin-like PCBs and total dioxins. In logistic regression analyses, the third and the highest quartiles of dioxin-like PCBs had adjusted odds ratios (ORs) of 3.07 (95% CI 1.16-8.81) and 6.82 (95% CI 2.59-20.1) compared to the reference (first plus second quartiles). On the other hand, the highest but not the third quartiles of PCDDs+PCDFs and total dioxins had significantly higher adjusted ORs compared to the respective references. These associations persisted when the subjects with poor liver or poor renal function were removed from the analysis. This recent representative data from general inhabitants in Japan showed associations of environmental exposure to dioxins, especially dioxin-like PCBs, with diabetes.
Hirokazu Uemura, Kokichi Arisawa, Mineyoshi Hiyoshi, Hiroshi Satoh, Yoshio Sumiyoshi, Kenji Morinaga, Kazunori Kodama, Taka-Ichiro Suzuki, Masaki Nagai and Tsuguyoshi Suzuki : PCDDs/PCDFs and dioxin-like PCBs: recent body burden levels and their determinants among general inhabitants in Japan., Chemosphere, Vol.73, No.1, 30-37, 2008.
(要約)
OBJECTIVE: The objective was to grasp the recent body burden levels of polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs) and dioxin-like polychlorinated biphenyls (DL-PCBs) and to investigate their determinants among general inhabitants in Japan. METHODS: This study was performed on 1374 participants aged 15-73 years, who were not occupational exposure to PCDDs/PCDFs and DL-PCBs, living widely in 75 different residential areas of 25 prefectures in Japan. Seven PCDDs, ten PCDFs, twelve DL-PCBs, which are assigned a toxicity equivalent factor, and biochemical factors were determined in fasting blood. A questionnaire survey on life-style was also performed. RESULTS: The median of total toxicity equivalent (TEQ) was 20pgTEQ/g lipid. The TEQs of PCDDs/PCDFs, DL-PCBs and total TEQ increased with age. The intake frequency of fish-and-shellfish was positively associated with the TEQ of DL-PCBs in both sexes. Current smoking was negatively related to the TEQ of DL-PCBs in male subjects but not in female subjects. Feeding status was significantly related to the TEQs of PCDDs/PCDFs, DL-PCBs and total TEQ, being lowest in breast feeding and highest in never and bottle feeding. According to the results of subgroup analysis, parity was not associated with the TEQs. CONCLUSIONS: The fish-and-shellfish consumption may contribute to the accumulation of DL-PCBs, and smoking may induce some biological action for the elimination of DL-PCBs from the human body. Breast feeding is considered to be one of the major excretory pathways of PCDDs/PCDFs and DL-PCBs in women, while parity may not largely contribute to the elimination of these pollutants.
Aya Fukumoto, Toshiaki Hashimoto, Hiromichi Ito, Mio Nishimura, Yoshimi Tsuda, Masahiro Miyazaki, Kenji Mori, Kokichi Arisawa and Shoji Kagami : Growth of head circumference in autistic infants during the first year of life, Journal of Autism and Developmental Disorders, Vol.38, No.3, 411-418, 2008.
(要約)
This study analyzed the increase in head circumference (HC) of 85 autistic infants (64 boys and 21 girls) during their first year of life. The data were collected from their "mother-and-baby" notebooks. This notebook is a medical record of the baby's growth and development delivered to the parents of all babies born in Japan. This is a retrospective study which gathered the data from the notebooks after the diagnosis of autism. However, none of the babies were known to have autism at the time the records were made. The head circumference at birth of these autistic children was similar to that of the average found in a Japanese Government Study of 14,115 children. However, it showed a marked increase at 1 month after birth. The discrepancy reached a peak at 6 months, while the difference became smaller at 12 months. Body length (BL) and body weight (BW) began to increase at 3 months, although at a rate smaller than the head circumference increase.
(キーワード)
Anthropometry / Autistic Disorder / Child Development / Head / Humans / Infant / Infant, Newborn
Hirokazu Uemura, Toshiyuki Yasui, Y Miyatani, M Yamada, Mineyoshi Hiyoshi, Kokichi Arisawa and Minoru Irahara : Circulating profiles of osteoprotegerin and soluble receptor activator of nuclear factor kappaB ligand in post-menopausal women., Journal of Endocrinological Investigation, Vol.31, No.2, 163-168, 2008.
(要約)
OBJECTIVE: The aim of this study was to elucidate the detail profiles of circulating osteoprotegerin (OPG) and soluble receptor activator of nuclear factor kappaB ligand (sRANKL) in post-menopausal women. METHODS: Eighty Japanese post-menopausal women were enrolled in this cross-sectional study. Circulating OPG and free fraction of sRANKL (free sRANKL), PTH, calcium and phosphorus, age, years since menopause, body mass index, bone mineral density of the vertebral bodies (LBMD) and bone turnover markers were determined in each subject. RESULTS: In rank order correlation analysis, serum OPG concentrations had a significant positive correlation with age (r=0.291, p=0.024) and a marginal significant negative correlation with LBMD (r=-0.247, p=0.062). However they did not have correlations with LBMD or other parameters after adjustment for age. Serum free sRANKL concentrations had a significant positive correlation with age (r=0.332, p=0.010) and a significant negative correlation with LBMD (r=-0.608, p<0.001). This correlation with LBMD persisted after adjustment for age. In a multiple regression analysis with a stepwise model, the main determinants of LBMD were age and serum free sRANKL (p=0.015 and p=0.006, respectively). CONCLUSIONS: We found the increase in circulating OPG and sRANKL with age and a robust negative correlation between circulating free sRANKL and LBMD after adjustment for age. The increase in circulating free sRANKL may reflect directly or indirectly the conditions coexistent with bone loss in post-menopausal women.
(キーワード)
Alkaline Phosphatase / Bone Density / Calcium / Collagen Type I / Female / Humans / Middle Aged / Osteoporosis, Postmenopausal / Osteoprotegerin / Parathyroid Hormone / Peptides / Phosphorus / Postmenopause / RANK Ligand / Solubility
(文献検索サイトへのリンク)
● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 18362509
Hirokazu Uemura, Toshiyuki Yasui, Yuka Miyatani, Masayo Yamada, Mineyoshi Hiyoshi, Kokichi Arisawa and Minoru Irahara : Circulating osteoprotegerin is associated with age and systolic blood pressure, but not with lipid profile or fasting glucose, in postmenopausal women., Menopause, Vol.15, No.1, 180-184, 2008.
(要約)
OBJECTIVE: Osteoprotegerin (OPG), an inhibitor of osteoclastogenesis and osteoclast activation, has been reported to be linked to vascular biology. The aim of this study was to clarify the relationships between circulating OPG and the risk factors for vascular disorders in postmenopausal women. DESIGN: Eighty Japanese postmenopausal women were enrolled in this cross-sectional study. Clinical parameters (age, number of years since menopause, body mass index, systolic and diastolic blood pressure); serum concentrations of OPG, creatinine, calcium, and phosphorus; serum lipid profile; plasma glucose; and bone mineral density of the L2-4 vertebral bodies were determined for each woman. RESULTS: In rank-order correlation analysis, serum OPG concentrations had significant positive correlations with age (r = 0.29, P = 0.03), systolic blood pressure (r = 0.45, P < 0.01), diastolic blood pressure (r = 0.34, P < 0.01), and serum creatinine (r = 0.29, P = 0.04). Serum OPG concentration also had a marginally significant negative correlation with bone mineral density of the L2-4 vertebral bodies (r = -0.25, P = 0.06). However, serum OPG did not correlate with body mass index, serum lipid profile, or plasma glucose. The correlation of serum OPG with systolic blood pressure persisted after adjustment for both age and serum creatinine. CONCLUSIONS: These results suggest that increased circulating OPG in postmenopausal women is closely related to higher systolic blood pressure, which could cause atherosclerosis.
(キーワード)
Age Factors / Atherosclerosis / Blood Glucose / Blood Pressure / Body Mass Index / Bone Density / Calcium / Creatinine / Cross-Sectional Studies / Female / Humans / Japan / Lipids / Middle Aged / Osteoprotegerin / Phosphorus / Postmenopause / Risk Factors
Kokichi Arisawa, Hirokazu Uemura, Mineyoshi Hiyoshi, Satoru Dakeshita, Atsushi Kitayama, Hiroshi Saito and Midori Soda : Cause-specific mortality and cancer incidence rates in relation to urinary 2-microglobulin: 23-year follow-up study in a cadmium-polluted area., Toxicology Letters, Vol.173, No.3, 168-174, 2007.
(要約)
A longitudinal study was performed to investigate the associations of exposure to environmental cadmium (Cd) with cause-specific mortality and cancer incidence rates. The study population comprised 275 adults living in a Cd-polluted area, Nagasaki Prefecture, Japan. The follow-up period extended from 1982 to 2005 for the analysis of cancer mortality, and from 1985 to 2002 for the analysis of cancer incidence. In the study area, the daily Cd intake from foods had decreased after 1980-1983 because of the restoration of Cd-polluted rice fields. The mortality rate among those with urinary beta2-microglobulin (U-beta2M)>/=1000 microg/g creatinine was significantly higher than that of the Japanese population for death from causes other than cancer, but not for cancers (177 at the 95% confidence interval [CI] 94-303). From analysis within the Cd-polluted area, the age-adjusted rate ratio of cancer deaths associated with increased U-beta2M was 2.58 (95% CI 1.25-5.36). The incidence rate of cancer among those with U-beta2M>/=1000 microg/g creatinine was 1.38 (95% CI 0.69-2.47) times that of the regional reference rate. Within the Cd-polluted area, the age-adjusted rate ratio of developing cancer associated with high U-beta2M was 1.79 (95% CI 0.84-3.82). In summary, there was a significant association between U-beta2M excretion and cancer mortality. However, there was neither a significantly increased standardized incidence ratio of cancer, nor significant relationship between U-beta2M and cancer incidence rate, though the point estimates were higher than unity. Continued follow-up and investigation of a larger cohort may be required before drawing a conclusion for the association between exposure to environmental Cd and cancer risk.
(キーワード)
Adult / Aged / Aged, 80 and over / Biological Markers / Cadmium Compounds / Environmental Pollutants / Female / Follow-Up Studies / Humans / Incidence / Japan / Male / Middle Aged / Neoplasms / Registries / Risk Assessment / Risk Factors / Time Factors / beta 2-Microglobulin
Kokichi Arisawa, Hirokazu Uemura, Mineyoshi Hiyoshi, Hideo Takeda, Hiroshi Saito and Midori Soda : Cadmium-induced renal dysfunction and mortality in two cohorts: diappearance of the association in a generation born later, Toxicology Letters, Vol.169, No.3, 214-221, 2007.
(要約)
The association between exposure to environmental cadmium and mortality was investigated in two cohorts. The study population consisted of 275 (cohort I) and 329 (cohort II) residents (aged >or=40 years) in a cadmium-polluted area, Nagasaki Prefecture, Japan, who had participated in health surveys conducted in 1982 and 1992, respectively. The follow-up period extended from 1982 or 1992 to 2005. In the study area, the dietary cadmium intake had decreased after 1980-1983 because of the restoration of cadmium-polluted paddy fields. In cohort I, the mortality rate among those with urinary beta2-microglobulin (beta2-MG) concentration >or=1000 microg/g creatinine (cr.) was 1.41 times higher than the regional reference rate (95% confidence interval [CI] 1.07-1.83). After adjusting for age and other variables, in men, urinary N-acetyl-beta-D-glucosaminidase, and in women, serum creatinine, beta2-MG clearance, and urinary beta2-MG were significantly associated with increased mortality. However, in cohort II, urinary beta2-MG or total protein was not significantly associated with survival. These findings indicate that cadmium-induced renal dysfunction was a significant predictor of mortality, but that such an association is disappearing, probably because of the selective loss of advanced cases and reduced exposure and body burden.
(キーワード)
Adult / Aged / Aged, 80 and over / Cadmium / Cohort Studies / Environmental Monitoring / Environmental Pollutants / Female / Health Surveys / Humans / Japan / Kaplan-Meier Estimate / Kidney Diseases / Male / Middle Aged / Proportional Hazards Models / Time Factors
Shinichiro Simbo, Naoko Matsuda-Inoguchi, Takao Watanabe, Kozue Sakurai, Chigusa Date, A Nishimura, Haruo Nakatsuka, Hiroshi Saito, Kokichi Arisawa and Masayuki Ikeda : Dietary intake of tin in Japan, and the effects on intake of canned food and beverage consumption, Food Additives and Contaminants, Vol.24, No.5, 535-545, 2007.
(要約)
The study reported herein was initiated to examine dietary tin intake (Sn-D) in Japan to elucidate the possible effects of consumption of canned food (including beverages) on Sn-D, and to compare the intake among regions and between the two sexes in reference to the current provisional tolerable weekly intake and intake in other countries. Urinary tin levels (Sn-U) were also studied. Duplicate diet samples (24 h) together with records of food intake were collected in 1999-2004 from 111 adult residents in four areas of Japan. After exclusion of incomplete samples, 95 valid samples were subjected to determination of tin by inductively coupled plasma mass spectrometry (ICP-MS) after acid digestion. Among the 95 cases, 37 women additionally provided urine samples. Distribution of Sn-D was markedly skewed. Median Sn-D was 5.6 microg day(-1) for total subjects, which was about one-tenth of the values previously reported for the Japanese population; the difference was most probably attributable to the difference in the methods of determination. Consumption of canned foods led to a substantial increase in Sn-D. Thus, the median Sn-D for canned food consumers of 35.7 microg day(-1), was eight-fold higher than the median Sn-D for non-consumers of 4.5 microg day(-1). Sn-U (as corrected for creatinine concentration) distributed log-normally with a geometric mean of 2.0 microg (g cr)(-1). No effect of canned food consumption was evident on Sn-U. When compared internationally, Sn-D for the Japanese population was substantially lower than Sn-D for populations in other industrialized countries.
(キーワード)
Female / Food Analysis / Food Contamination / Food Preservation / Humans / Japan / Male / Spectrophotometry, Atomic / Tin
To elucidate the mortality characteristics of Tokushima Prefecture, the authors analyzed thetime-related change in the standardized mortality ratio (SMR) of cause-specific death and organspecificcancer death during 1983-2002, and administrative area-specific SMR during 1993-1998 and1999-2002. The gender-and 5-year-age-specific and cause-specific death rates in the entire Japanesepopulation were used as the reference mortality, and the population of sex-and-5-year-agespecificcategory in the census year(1985, 1990, 1995 and 2000)was used as the population ofTokushima Prefecture. Interval estimation of SMR was performed by the exact method, assumingthat the number of deaths followed the Poisson distribution. In the analysis of each year from1983 to 2002, the SMR of diabetes mellitus markedly increased from the mid 1990's, suggesting thechanges in the environmental factors. The SMR of bronchitis, emphysema and asthma wasconstantly high during the 20 years. In the administrative area-specific analysis, the SMR ofdiabetes was high in Tokushima and Naruto for both men and women. With regard to malignantneoplasms, the SMR of esophageal cancer was constantly low, while that of liver cancer wasconstantly high over the 20 years. The SMR of esophageal cancer was low among men inTokushima and Anan, and among women in Kamojima, while that of liver cancer was high amongmen and women in Tokushima and among men in Anan. These characteristics were consistentover the recent 10 years, suggesting the involvement of area-specific factors.
(キーワード)
diabetes / esophageal cancer / geographic distribution / liver cancer / standardized mortality ratio / time trend
Recent progress in life science technology and the availability of much information on genes obtained by genome analysis has enabled us to analyze the changes of proteins on a large scale. Sets of proteins are called proteomes, and proteomics is the scientific field of proteome analysis including differential, post translational modification and interaction analyses. Various proteomic techniques, particularly two-dimensional gel electrophoresis (2-DE), mass spectrometry, protein chip methods, and surface plasmon resonance (SPR), are very useful for acquiring proteomes in cells, tissues and body fluid, and for analyzing interactions between a protein and other biofactors including proteins. A proteomic approach is also useful for determining biomarkers of diseases and key proteins involved in various stages of metabolism such as differentiation, cell cycle and apoptosis. Environmental pollutants including endocrine disruptors inhibit activities of various organs in wild animals and humans. Proteomic approaches could be very useful tools for elucidating the mechanisms of damage caused by environmental pollutants. In this review, we describe the application of a proteomic approach to the field of environmental medicine.
Kokichi Arisawa, Midori Soda, Masazumi Akahoshi, Saeko Fujiwara, Hirokazu Uemura, Mineyoshi Hiyoshi, Hideo Takeda, Wataru Kashino and Akihiko Suyama : Human T-cell lymphotropic virus type-1 infection and risk of cancer: 15.4 year longitudinal study among atomic bomb survivors in Nagasaki, Japan, Cancer Science, Vol.97, No.6, 535-539, 2006.
(要約)
The objective of the present study was to investigate the association between human T-lymphotropic virus type-1 (HTLV-1) infection and cancer risk in a longitudinal study. The study population consisted of 2729 atomic bomb survivors in Nagasaki Prefecture, Japan, who had no previous history of cancer at baseline. The baseline survey, including analysis of antibody to HTLV-1, took place during 1985-1987 and follow-up was performed until the end of 2001. There were 553 incident cases of malignant neoplasms during the observation period. After adjustment for sex, age and other variables, HTLV-1 infection was not associated with the risk of developing cancers of all sites, excluding adult T-cell leukemia (rate ratio 1.0, 95% confidence interval [CI] 0.76-1.4), stomach, colon and rectum, lung, female breast or other minor sites, but was associated with increased risk of liver cancer (rate ratio 2.1, 95%CI 1.0-4.6). The point estimate of the rate ratio for thyroid cancer was 3.0, but this was not significantly higher than 1 because of the small number of events (n = 11) and low prevalence of HTLV-1 seropositivity. These findings support the idea that HTLV-1 infection is not associated with an increased general cancer risk. Confounding by hepatitis C virus (HCV) and the interaction between HTLV-1 and HCV may explain the increased risk of liver cancer among HTLV-1 carriers. Further follow-up may be required to determine if HTLV-1 carriers are at increased risk of thyroid cancer.
Osamu Nakagomi, Toyoko Nakagomi and Kokichi Arisawa : A lack of significant association between the electropherotype or G-serotype of the infecting strain and disease severity of rotavirus gastroenteritis., Archives of Virology, Vol.151, No.10, 1947-1960, 2006.
(要約)
Despite many previous studies, the question has not been settled as to whether some human rotavirus strains are more virulent than others. Since disease severity is most clearly reflected by the hospitalization status of the infected children, we examined whether there was any difference in the distribution of dominant strains between inpatient and outpatient groups. The study population comprised 763 children with acute diarrhea who were treated at a general hospital in Honjo City, Akita, Japan, during 1986-1997. Rotaviruses from stool specimens were classified into 77 electropherotypes using polyacrylamide gel electrophoresis. A single dominant strain or two co-dominant strains circulated simultaneously with some infrequent strains in most rotavirus seasons. Over the 11 rotavirus seasons, there was no significant difference in the relative frequencies of 15 rotavirus strains between the inpatient and the outpatient groups when strains of rotavirus were defined by their electropherotypes in polyacrylamide gel electrophoresis. However, infection with one G1 strain that co-dominated with a G4 strain carrying an identical electropherotype except the VP7 gene resulted in a statistically significantly reduced risk of hospitalization. There was no significant difference in the relative frequencies of four major G-serotypes or long/short RNA pattern. We conclude that the virulence or disease-causing potential of human rotavirus is not substantially different in the majority of strains.
To clarify the characteristics of mortality in Tokushima Prefecture, the authors analyzed thestandardized mortality ratio(SMR)from 1993 to 1998 and 1999 to 2002. The sex-and 5-year-agespecificand cause-specific morality rates in Japan were used as the standard mortality, and thepopulation of sex-and 5-year-age-specific category in the census year(1995 and 2000)was used asthe population of Tokushima Prefecture. The 95 % confidence interva(l CI)of SMR was estimatedusing the exact method, on the assumption that the number of deaths followed the Poisson distribution.The mortality from all-cause in Tokushima Prefecture was significantly lower than that of theentire Japanese population among women during 1993-1998, while it was significantly higheramong men and women during 1999-2002. The SMRs of diabetes mellitus, bronchitis, emphysemaand asthma, and chronic hepatitis and liver cirrhosis were significantly higher than 100, with theSMR of diabetes being as high as 130-140. On the other hand, mortality rate from suicide was significantlylower than that of all of Japan. Regarding malignant neoplasms, morality rates fromcancers of all sites, esophagus, stomach, and colon and rectum were significantly lower than 100.However, the SMR of liver cancer was significantly high, suggesting that hepatitis C virus infectionwas endemic. The reason for the high mortality from diabetes should be clarified with regard toenvironmental and genetic factors, and the way of reporting diabetes as a cause of death in deathcertificates. In addition, the reason for the low mortality from cancers of the gastrointestinal tractremains unknown, and further investigations on life style factors are required.
(キーワード)
1993年 / standardized mortality ratio / diabetes / liver cancer / esophageal cancer / gastric cancer
Toyoko Nakagomi, Y Takahashi, Kokichi Arisawa and Osamu Nakagomi : A high incidence of intussusception in Japan as studied in a sentinel hospital over a 25-year period (1978-2002), Epidemiology and Infection, Vol.134, No.1, 57-61, 2006.
(要約)
The development of second-generation rotavirus vaccines requires knowledge of baseline incidence rates for intussusception in infants prior to vaccine introduction. To obtain such estimates we reviewed clinical records in a hospital that served as the major provider of paediatric beds in a local community in the northern part of Japan. During the 25-year period (1978-2002), there were 91 hospitalizations due to radiologically confirmed intussusception in children <5 years of age, of which 45% were <1 year of age. Assuming that all children with intussusception in the area had been admitted to this hospital, there were an average of 185 and 78 hospitalizations per 100000 person-years for children <1 year old and 5 years old respectively. There was period-to-period variability with no long-term secular trend in the incidence of intussusception. The incidence rate in Japan was among the highest thus far reported, providing further evidence of geographic variability.
Kotaro Takazawa and Kokichi Arisawa : Relationship between the type of urinary incontinence and falls among frail elderly women in Japan., The Journal of Medical Investigation : JMI, Vol.52, No.3,4, 165-171, 2005.
(要約)
Urinary incontinence and falls are serious problem among elderly people, because of restriction of the Activities of Daily Living (ADL) and Quality of Life. Previous studies have examined the association between urinary incontinence and falls. However, results have been inconsistent. In Japan, with the rapid aging of the society, the number of elderly women who have urinary incontinence and are at risk of falling is increasing. We investigated the relationship between type of urinary incontinence and risk of falls among elderly users of day-care services in a long-term care system. Our study population comprised 118 ambulatory women. At baseline, we evaluated incontinent status, lower extremity muscle strength, balance ability, ADL, and Instrumental ADL. We asked subjects about number of falls every 4 months during a year. In univariate analysis, lower extremity muscle strength (p = 0.001) and mixed incontinence (p = 0.050) differed significantly according to the fall status. Stress and urge incontinence were not significantly associated with falls. In logistic regression analysis, subjects who had mixed incontinence were 3.05 (95% confidence interval 1.01-10.2) times more likely to fall than those without. These results suggest that mixed incontinence have independent associations with falls. Incontinent status should be considered to prevent falls among elderly persons who are partially dependent and need support.
(キーワード)
Accidental Falls / Activities of Daily Living / Aged / Female / Frail Elderly / Humans / Japan / Muscle Weakness / Risk Factors / Urinary Incontinence
Kokichi Arisawa, Hideo Takeda and Hiroaki Mikasa : Background exposure to PCDDs/PCDFs/PCBs and its potential health effects: a review of epidemiologic studies, The Journal of Medical Investigation : JMI, Vol.52, No.1,2, 10-21, 2005.
(要約)
Here we review epidemiologic studies dealing with the dietary intake and the body burden of polychlorinated dibenzo-p-dioxins (PCDDs)/polychlorinated dibenzo-furans (PCDFs)/ polychlorinated biphenyls (PCBs) in the general population, and potential adverse health effects of these substances, especially on the risk of diabetes mellitus and endometriosis, and on thyroid function and the neurodevelopment of infants. The mean or median intake of dioxin-related compounds among the general populations of various countries is lower than the maximum tolerable daily intake (TDI) set by the WHO in 1998 (4pg TEQ/kg/day). However, there have been few reports on the distribution of intake and the proportion of subjects whose exposure levels exceed the maximum TDL. At present, it remains unclear whether background exposure to dioxin-related compounds is associated with increased risk of diabetes (because of lack of longitudinal studies), endometriosis (because of lack of studies with sufficient statistical power), or altered thyroid function (because of inconsistent results on humans). Consistent results have been reported for the association between exposure to background levels of PCBs/dioxins, especially trans-placental PCBs, and defective neurodevelopment of infants in the U.S. and Europe. Thus, efforts should be made to further decrease the body burden among women of reproductive age by reducing the release of PCDDs/PCDFs/PCBs into the environment.
Yoichi Hirakata, Kokichi Arisawa, Osamu Nishio and Osamu Nakagomi : Multi-prefectural spread of gastroenteritis outbreaks attributable to a single genogroup II norovirus strain from a tourist restaurant in Nagasaki, Japan., Journal of Clinical Microbiology, Vol.43, No.3, 1093-1098, 2005.
(要約)
A series of gastroenteritis outbreaks caused by noroviruses (NVs) among tourist groups from several prefectures was associated with eating a lunch prepared by a restaurant in Nagasaki City, Japan, on 18 and 19 November 2003. A retrospective cohort study was performed to estimate the magnitude of the outbreak and identify the source of infection. Epidemiological information was obtained through the local public health centers in the areas where the illness occurred. Stool and vomit specimens and food and environmental samples were analyzed by reverse transcription-PCR with genogroup-specific primers. Positive samples were sequenced and analyzed phylogenetically. Of 1,492 tourists who ate a lunch prepared by the restaurant during the 2-day period, 660 (44.2%) developed illness, with an average incubation time of 31.2 h. Whereas NVs were not detected in any food samples, identical sequences most closely related to the Mexico genotype of genogroup II NV were found in specimens from case patients, restaurant staff, and the kitchen table. Food handlers were concluded to be the source of the outbreak as a result of the contamination of several meals. The series of outbreaks described here exemplifies the role of tourism as a contemporary way to distribute a single infectious agent to multiple and geographically remote areas.
Noboru Takamura, Tatsuro Kondoh, Syohei Ohgi, Kokichi Arisawa, Mariko Mine, Shunichi Yamashita and Kiyoshi Aoyagi : Abnormal folic acid homocysteine metabolism as maternal risk factors for Down syndrome in Japan., European Journal of Nutrition, Vol.43, No.5, 285-287, 2004.
(要約)
Japan has been considered as "a folate sufficient area", since traditional Japanese food contains an adequate amount of folic acid. However, the recent westernized food style of young Japanese mothers may affect the intake of folic acid among them. This food style may contribute to the occurrence of Down syndrome, which has proved to be linked to abnormal folate and homocysteine metabolisms. To preliminarily evaluate the levels of folic acid,homocysteine and other relevant factors which are associated with folate metabolism, among Japanese women who had pregnancies affected by Down syndrome. Blood samples from 31 women who had pregnancies affected by Down syndrome (DS) were obtained. 60 age-matched control blood samples were also obtained from mothers who had not experienced miscarriages or abnormal pregnancies (CONT). Plasma homocysteine and serum folic acid, vitamin B12, and B6 were measured and compared between DS and CONT. Furthermore, the frequency of MTHFR polymorphism (C677T) was also investigated. Plasma levels of homocysteine were significantly increased in DS mothers (p = 0.004). In contrast, serum levels of folic acid were significantly decreased in DS mothers (p = 0.0001). There were no significant differences in the vitamin B12 and B6 levels between DS and CONT. Also, the frequency of 5,10-methylenetetrahydrofolate reductase gene (MTHFR) homozygous polymorphism showed no differences between DS and CONT. Different levels of serum folic acid and plasma homocysteine between both groups may contribute to the occurrence of Down syndrome even in Japan. Although there was no significant difference in the frequency of MTHFR polymorphism between the groups, probably because of an inadequate number of samples, further studies may contribute to the understanding of the occurrence of Down syndrome in Japan.
(キーワード)
Adult / Down Syndrome / Female / Folic Acid / Homocysteine / Humans / Japan / Methylenetetrahydrofolate Reductase (NADPH2) / Polymorphism, Genetic / Pregnancy / Risk Factors / Vitamin B 12 / Vitamin B 6
Toshiyuki Mikami, Toyoko Nakagomi, Rika Tsutsui, Kazuko Ishikawa, Yohko Onodera, Kokichi Arisawa and Osamu Nakagomi : An outbreak of gastroenteritis during school trip caused by serotype G2 group A rotavirus., Journal of Medical Virology, Vol.73, No.3, 460-464, 2004.
(要約)
Between May14 and 18, 2001, there was an outbreak of acute gastroenteritis involving 45 school children out of a total of 107 (aged 11-12 years) attending a 3-day school trip. The epidemic curve characterized by a rapid onset and decline with a single peak incidence over a 5-day period resembled the pattern typical of a food-borne gastroenteritis outbreak. Epidemiological and virological investigations concluded, however, that this outbreak was caused by a single strain of serotype G2 group A rotavirus spreading to schoolmates from the primary case-pupil who had already been ill at the start of the trip. Efficient person-to-person transmission was likely to have occurred due to prolonged and close contacts under the conditions typical of such school trips. This study emphasizes the importance of including group A rotavirus infection as a possible cause of gastroenteritis outbreaks even in older children and adults.
Michiyo Yokoo, Kokichi Arisawa and Osamu Nakagomi : Estimation of annual incidence, age-specific incidence rate, and cumulative risk of rotavirus gastroenteritis among children in Japan, Japanese Journal of Infectious Diseases, Vol.57, No.4, 166-171, 2004.
(要約)
Rotavirus gastroenteritis is a common childhood infection, but the exact morbidity of the disease is not well described in Japan. We aimed at estimating morbidity measures to determine the magnitude of rotavirus gastroenteritis. An estimate for acute infectious gastroenteritis of all causes, to which rotavirus gastroenteritis belongs, has been available since the enactment in 1999 of the Law concerning the Prevention of Infectious Diseases and Medical Care of Patients with Infectious Diseases. Using this estimate and another estimate for the detection proportion of rotavirus among outpatients with acute infectious gastroenteritis, we calculated the annual incidence, the age-specific annual incidence rate, and the cumulative risk by the age of 6 years for rotavirus gastroenteritis. The latter estimate was obtained by a meta-analysis of four independent studies previously performed in Japan. According to our estimates, approximately 800,000 children in Japan under the age of 6 years visit pediatric practices or the outpatient department of hospitals because of rotavirus gastroenteritis at a rate of 11 cases/100 persons/year, and one in two children will visit pediatricians before they go to primary school. Such pediatrician visits most frequently occur at the age of 1 year (27 cases/100 persons/year). Thus, the magnitude of the burden of rotavirus disease among Japanese children is substantial.
Syohei Ohgi, Tomitaro Akiyama, Kokichi Arisawa and Kenta Shigemori : Randomized controlled trial of swaddling versus massage in the management of excessive crying in infants with cerebral injuries., Archives of Disease in Childhood, Vol.89, No.3, 212-216, 2004.
(要約)
Infants with neonatal cerebral insults are susceptible to excessive crying as a result of difficulties with self-regulation. To compare the effectiveness of swaddling versus massage therapy in the management of excessive crying of infants with cerebral insults. Randomised three-week parallel comparison of the efficacy of two intervention methods. Infants with symptoms of troublesome crying and their parents were randomly assigned to a swaddling intervention group (n = 13) or a massage intervention group (n = 12). The amount of total daily crying decreased significantly in the swaddling group, but did not decrease significantly in the massage group. Infant behavioural profiles and maternal anxiety levels improved significantly in the swaddling group post-intervention. Parents in the swaddling group were more satisfied with the effectiveness of the intervention in reducing crying than parents in the massage group. Results indicate that swaddling may be more effective than massage intervention in reducing crying in infants with cerebral injuries.
(キーワード)
Attitude to Health / Birth Injuries / Brain Injuries / Crying / Female / Humans / Infant / Infant Care / Infant, Newborn / Male / Massage / Parents / Restraint, Physical / Time Factors
Sakae Nagaoka, Hiroshi Yatsuhashi, Hisayuki Hamada, Koji Yano, Takehiro Matsumoto, Manabu Daikoku, Kokichi Arisawa, Hiromi Ishibashi, Michiaki Koga, Michio Sata and Michitami Yano : The des-gamma-carboxy prothrombin index is a new prognostic indicator for hepatocellular carcinoma., Cancer, Vol.98, No.12, 2671-2677, 2003.
(要約)
Des-gamma-carboxy prothrombin (DCP) has been reported to be an important prognostic factor in patients with hepatocellular carcinoma (HCC). Recently, a monoclonal antibody, 19B7, which recognizes the Gla domain of DCP, has been identified. The 19B7 antibody recognizes an epitope different from that recognized by MU-3, which is another antibody against DCP. In this study, the authors investigated the measurement of DCP using the antibodies MU-3 and 19B7, respectively, as a prognostic factor for patients with HCC who had solitary, small tumors and or Child Stage A HCC. One hundred four patients with HCC who had solitary, small tumors or Child Stage A tumors were enrolled in the study between 1991 and 2001. All patients were treated and were followed for a mean of 3.2 years. The authors analyzed the correlation between the DCP Index (DCP measured by MU-3 and DCP measured by 19B7) and patient prognosis. The patients were classified into 3 groups based on their DCP Index: 1) DCP negative (DCP < 40 milli arbitrary unit (mAU)/mL)); 2) low DCP Index (DCP > or = 40 mAU/mL; MU-3:19B7 ratio, < 3.0; and 3) high DCP Index (DCP > or = 40 mAU/mL; MU-3:19B7 ratio, > or = 3.0). The survival rate for patients in the high DCP Index group was lower compared with the survival rate for patients in the DCP-negative group and was significantly lower compared with the survival rate for patients in the low DCP Index group. In a univariate Cox proportional hazards model, the positive factors were high DCP Index and low DCP Index. Among the positive predictive factors that were analyzed using a multivariate Cox proportional hazards model were age (hazard ratio, 3.27; P = 0.006), low DCP Index (hazard ratio, 2.87; P = 0.012), and high DCP Index (hazard ratio, 12.3; P < 0.0001). The prognosis of patients who had a high DCP Index score was poorer compared with patients who had a low DCP Index score and patients who were classified as DCP negative. The authors concluded that the DCP Index is a prognostic indicator for patients with HCC.
Kokichi Arisawa, Tomotaka Sobue, Itsuro Yoshimi, Midori Soda, Satoshi Shirahama, Hiroshi Doi, Shigeru Katamine, Hiroshi Saito and Minoru Urata : Human T-lymphotropic virus type-I infection, survival and cancer risk in southwestern Japan: A prospective cohort study., Cancer Causes & Control, Vol.14, No.9, 889-896, 2003.
(要約)
This study prospectively evaluated the associations of human T-lymphotropic virus type-I (HTLV-I) infection with survival and cancer incidence. The study base comprised 4297 adults (aged 40-69 years in 1993) who had either visited the outpatient clinic or who had received annual health check-ups at the A Hospital, Nagasaki, Japan, between 1985 and 1992 (HTLV-I seropositivity = 24.7%). During the follow-up period (1993-1999 or 2000), 290 deaths and 261 cases of malignant neoplasms occurred, including ten deaths and six incident cases of adult T-cell leukemia/lymphoma (ATL). After adjustment for gender, age and other covariates, HTLV-I seropositivity was associated with an increased mortality from all-causes excluding ATL (rate ratio, RR = 1.3, 95% confidence interval, CI = 1.0-1.7), all non-neoplastic diseases (RR = 1.5, 95% CI = 1.0-2.3) and heart diseases. HTLV-I infection was not found to be associated with an increased risk of developing total cancers other than ATL (RR = 0.98, 95% CI = 0.74-1.3), colorectal cancers, liver cancer or lung cancer, but was associated with a reduced risk of gastric cancer (RR = 0.42, 95% CI = 0.17-0.99). HTLV-I infection is associated with increased mortality from all-causes excluding ATL and all non-neoplastic diseases. HTLV-I carriers may not be at increased general cancer risk, but at reduced risk of gastric cancer.
(キーワード)
Aged / Cause of Death / Cohort Studies / Female / Food Habits / HTLV-I Infections / Human T-lymphotropic virus 1 / Humans / Incidence / Japan / Leukemia-Lymphoma, Adult T-Cell / Male / Middle Aged / Neoplasms / Proportional Hazards Models / Prospective Studies / Questionnaires / Risk Factors / Survival Analysis
Shohei Ohgi, Tatsuya Takahashi, Kevin J Nugent, Kokichi Arisawa and Tomitaro Akiyama : Neonatal behavioral characteristics and later behavioral problems., Clinical Pediatrics, Vol.42, No.8, 679-686, 2003.
(要約)
The purposes of this study were (1) to evaluate the usefulness of the Neonatal Behavioral Assessment Scale (NBAS) as a tool to assess the risk of later behavioral problems, (2) to analyze the relationship between neonatal behavioral characteristics and behavioral problems in childhood. Subjects were 77 very-low-birth-weight infants admitted to the NICU at the Nagasaki University Hospital, Nagasaki, Japan. The results suggest that behavioral characteristics such as poor motor performance, poor state regulation, and poor interaction ability in the neonatal period are risk factors for behavioral problems in childhood. The NBAS could help clinicians to identify neonates at risk of later behavioral problems.
Shohei Ohgi, Kokichi Arisawa, Tomitaro Akiyama, Tatsuya Takahashi, Yoshiko Goto and Hiroshi Saito : Neonatal Behavioral Assessment Scale as a predictor of the later developmental disabilities of low birth-weight and/or premature infants., Brain & Development, Vol.25, No.5, 313-321, 2003.
(要約)
The purpose of this study was to evaluate the usefulness of the Neonatal Behavioral Assessment Scale (NBAS) as a tool to assess the risk of later developmental disabilities. The study subjects were 209 low birth-weight and/or premature infants admitted to the NICU at the Nagasaki University Hospital, Nagasaki, Japan. These infants were examined using the NBAS at 36-38 (NBAS36), 40-42 (NBAS40) and 44-46 weeks (NBAS44) of postmenstrual age, and their developmental outcome was measured using standardized assessments at 5 years of age. Based on the results of diagnosis at 5 years of age, subjects were classified into three groups: Normal, Mild Disability and Severe Disability groups. Multinomial logistic regression analysis showed that lower Motor cluster scores for all assessment periods and lower Orientation cluster scores in the NBAS40 and NBAS44 were significantly associated with an increased risk of both Mild and Severe Disability. Also, the Range of State cluster scores for the NBAS44 were significantly related to the risk of Mild Disability, and the Reflexes cluster scores in the NBAS40 and NBAS44 were the best predictor of Severe Disability. In outcome prediction using the estimated regression coefficients, 94-97% of the subjects in the Normal group, 50-78% in the Mild Disability group and 71-85% in the Severe Disability group were correctly classified. The NBAS could help clinicians to develop a management protocol for infants at risk for developmental disabilities as well as to identify neonates at risk of developmental disabilities.
Tohru Nakagoe, Terumitsu Sawai, Takashi Tsuji, Masa-aki Jibiki, Atsushi Nanashima, Hiroyuki Yamaguchi, Toru Yasutake, Hiroyoshi Ayabe and Kokichi Arisawa : Preoperative serum level of CA19-9 predicts recurrence after curative surgery in node-negative colorectal cancer patients., Hepato-Gastroenterology, Vol.50, No.51, 696-699, 2003.
(要約)
We hypothesize that a subset of node-negative colorectal cancer patients exists that is at high risk for recurrence after curative surgery. Preoperative serum levels of sialyl Lewisa (CA19-9), sialyl Lewisx (SLX), sialyl Tn (STN), and carcinoembryonic (CEA) antigens were analyzed for their value in predicting for such a group. One-hundred-forty-five patients with node-negative, T1-4, M0 colorectal cancers were divided into groups of low or high serum antigen levels. Disease-free interval served as the endpoint in evaluating the prognostic strength of each variable. Twenty-seven patients (18.6%) were included in the high group for CA19-9 antigen, 11 (7.6%) for SLX, 13 (9.0%) for STN, and 51 (35.2%) for CEA. The median follow-up was 62.1 months. As compared to those with low levels, patients with elevated CA19-9 had a shorter disease-free interval (P = 0.0026). No significant difference in disease-free interval was noted between low and high groups of SLX, STN, and CEA antigens. Cox regression analysis identified elevated serum CA19-9 level as a predictor for decreased disease-free interval, independent of T-stage or tumor location. Elevated preoperative serum levels of CA19-9 may serve as a useful marker in identifying patients with node-negative colorectal cancers at high risk for recurrence after surgery.
(キーワード)
Adenocarcinoma / Adult / Aged / Aged, 80 and over / CA-19-9 Antigen / Colorectal Neoplasms / Disease-Free Survival / Female / Humans / Lymphatic Metastasis / Male / Middle Aged / Neoplasm Recurrence, Local / Neoplasm Staging / Predictive Value of Tests / Tumor Markers, Biological
(文献検索サイトへのリンク)
● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 12828063
Kotaro Takazawa, Kokichi Arisawa, Sumihisa Honda, Yoshisada Shibata and Hiroshi Saito : Lower-extremety muscle forces measured by a hand-held dynamometer and the risk of falls among day-care users in Japan., Disablity and Rehabilitation, Vol.25, No.8, 399-404, 2003.
152.
Kokichi Arisawa, Toru Matsumura, Chiharu Tohyama, Hiroshi Saito, Hiroshi Satoh, Masaki Nagai, Masatoshi Morita and Tsuguyoshi Suzuki : Fish intake, plasma omega-3 polyunsaturated fatty acids, and polychlorinated dibenzo-p-dioxins (PCDDs)/polychlorinated dibenzo-furans (PCDFs) and coplanar polychlorinated biphenyls (co-PCBs) in the blood of the Japanese population., International Archives of Occupational and Environmental Health, Vol.76, No.3, 205-215, 2003.
(要約)
To evaluate background exposure levels and determinants of the individual variations in the exposure to dioxins in Japan. A cross-sectional study was performed on 131 men and 122 women (aged 20-76 years), who resided in five prefectures of Japan and had no occupational exposure to dioxins. Seven polychlorinated dibenzo-p-dioxins (PCDDs), ten polychlorinated dibenzo-furans (PCDFs) and 12 polychlorinated biphenyls (PCBs), which are assigned a toxicity equivalent factor, were determined in fasting blood. Biochemical analysis of plasma and a questionnaire survey on life-style, including dietary habit, were also performed. Factors associated with the levels of dioxin-related compounds in blood were evaluated by multiple linear regression. The median of total toxicity equivalents (TEQs) in men and women was 17 and 16 pg TEQ/g lipid, respectively, with no gender difference. After adjustment for age and other covariates, plasma concentrations of eicosapentaenoic acid, a biomarker of fish intake, were found to be positively associated with blood levels of total dioxin, PCDDs, PCDFs and PCBs, all of which were expressed on a TEQ basis (P<0.01). The frequency of intake of coastal fish, such as horse mackerel, mackerel and sardine, was also associated with TEQ-based concentrations of PCDFs (P=0.03) and PCBs (P=0.08). The intake of raw fish was positively related to total dioxins (P=0.06) and PCBs (P=0.03). The level of intake of marine fish, especially raw fish and coastal varieties, may be associated with increased blood levels of dioxin-related compounds among the population. Despite high fish consumption in Japan, the body burden of dioxins in the population was not found to be higher than that in western countries.
Tohru Nakagoe, Takashi Tsuji, Terumitsu Sawai, Kazuyuki Sugawara, Naoko Inokuchi, Shimeru Kamihira and Kokichi Arisawa : Minilaparotomy may be independently associated with reduction in inflammatory responses after resection of colorectal cancer., European Surgical Research, Vol.35, No.6, 477-485, 2003.
(要約)
A minilaparotomy approach (skin incision less than 7 cm) to resection of colon cancer is technically feasible, but objective data supporting its benefit are scarce. The aim of this study was to clarify whether minilaparotomy is independently associated with a reduction in the acute inflammatory response after resection of colorectal cancer. Thirty-one patients who underwent surgical resection of colorectal cancer using minilaparotomy or conventional laparotomy were included in this nonrandomized prospective study. Inflammatory responses were evaluated with serum interleukin-6 (IL-6) and C-reactive protein (CRP) levels. In both the minilaparotomy and conventional laparotomy groups, serum IL-6 and CRP levels significantly increased 24 h after the operation (1POD) compared to preoperative levels (p < 0.0001 and p < 0.0001, respectively). Median serum levels of IL-6 and CRP in the minilaparotomy group were significantly lower at 1POD versus the conventional group (p = 0.0066 and p = 0.0033, respectively). Multivariate analyses showed that a smaller increase in serum IL-6 or CRP levels at 1POD [less than 75th percentile (112.9 or 10.6 mg/ml, respectively)] was independently related to only minilaparotomy. These data in this nonrandomized trial suggest that minilaparotomy may be independently associated with reduced inflammatory responses in colorectal cancer resection.
Kokichi Arisawa, Midori Soda, Satoshi Shirahama, Hiroshi Saito, Noboru Takamura, Maki Yamaguchi, Kazumasa Odagiri, Tohru Nakagoe, Akihiko Suyama and Hiroshi Doi : Geographic distribution of the incidence of adult T-cell leukemia/lymphoma and other malignancies in Nagasaki Prefecture, Japan., Japanese Journal of Clinical Oncology, Vol.32, No.8, 301-306, 2002.
(要約)
It remains unclear whether human T-cell lymphotropic virus type-I (HTLV-I) infection is associated with an increased risk of malignancies other than adult T-cell leukemia/lymphoma. The authors investigated the geographic distribution of the incidence of adult T-cell leukemia/lymphoma and other malignancies in Nagasaki Prefecture, Japan, where HTLV-I is endemic. The world age-standardized incidence rates of adult T-cell leukemia/lymphoma and five cancers of other sites were calculated in 15 areas, using the data from the Nagasaki Prefectural Cancer Registry (1985-97). The incidence of adult T-cell leukemia/lymphoma was found to be positively correlated with that of biliary tract cancer in men (person-years-weighted r = 0.49, P = 0.06) and liver cancer in women (r = 0.56, P = 0.03), but not with cancer of the stomach, lung or cervix uteri. The results may not support the hypothesis that HTLV-I infection is strongly associated with an increased risk of cancer of the stomach, lung or cervix uteri. The association between HTLV-I infection and cancer of the biliary tract and the possible interaction between hepatitis C virus and HTLV-I in the development of liver cancer should be evaluated by prospective cohort studies.
(キーワード)
Adult / Age Distribution / Aged / Biliary Tract Neoplasms / Carcinoma, Small Cell / Female / Geography / Humans / Incidence / Japan / Leukemia-Lymphoma, Adult T-Cell / Liver Neoplasms / Lung Neoplasms / Male / Middle Aged / Risk Factors / Sex Factors / Stomach Neoplasms
Shohei Ohgi, Masafumi Fukuda, Hiroyuki Moriuchi, Takashi Kusumoto, Tomitaro Akiyama, Kevin J Nugent, Berry T Brazelton, Kokichi Arisawa, Tatsuya Takahashi and Hiroshi Saito : Comparison of Kangaroo Care and standard care: Behavioral organization, development and temperament in healthy low-birth-weight infants through one year., Journal of Perinatology, Vol.22, No.5, 374-379, 2002.
(要約)
To determine whether Kangaroo Care (KC) for healthy, low-birth-weight (LBW) infants can promote better behavioral and developmental outcomes. In this historical control study, 26 infants in the KC group (GA: 34.3+/-2.5 weeks, BW: 1833.9+/-167.6 g) and 27 infants in the comparison group who received the standard medical-nursing care (34.6+/-2.3 weeks, 1850.9+/-156.7 g) were analyzed by the Neonatal Behavioral Assessment Scale (NBAS) at 40 weeks of postmenstrual age, the Bayley Scales of Infant Development and the Carey's Infant Temperament Questionnaire (ITQ) at 6 and 12 months corrected ages. KC infants had significantly higher NBAS scores in Orientation, State Regulation, and Supplementary items; lower Intensity scores and higher Mood scores at 6 months on the ITQ; and higher Bayley Scales score at 12 months. KC effectively promoted neonatal behavioral organization and enhanced developmental outcome over the first year of life for LBW infants.
(キーワード)
Birth Weight / Child Development / Female / Humans / Infant Behavior / Infant Care / Infant, Newborn / Male / Mother-Child Relations / Temperament / Touch
Tohru Nakagoe, Terumitsu Sawai, Takashi Tsuji, Masaaki Jibiki, Atsushi Nakashima, Hiroyuki Yamaguchi, Toru Yasutake, Hiroyoshi Ayabe, Kokichi Arisawa and Hiroshi Ishikawa : Difference in prognostic value between sialyl Lewis (a) and sialyl Lewis (x) antigen levels in the preoperative serum of gastric cancer patients., Journal of Clinical Gastroenterology, Vol.34, No.4, 408-415, 2002.
(要約)
Sialyl Lewis(a) (CA19-9) and sialyl Lewis(x) antigens (SLX) may play a role in tumor metastasis by serving as functional ligands in the cell adhesion system. The authors examined preoperative serum levels of CA19-9 and SLX in 218 patients who underwent resection for gastric cancer to determine their prognostic value. The patients were divided into two groups, termed the low and high antigen groups, based on a value selected as a diagnostic cutoff. Correlation between the antigen serum levels, various established clinicopathologic factors, and prognosis were studied by univariate and multivariate analysis. The disease-specific interval for high CA19-9 and SLX groups was significantly shorter than that of their respective low groups (p = 0.0024 and p < 0.0001, respectively). Patients with stage III/IV tumors who had high serum SLX levels had shorter disease-specific intervals than those with low serum levels (p = 0.0017). A Cox's regression analysis revealed a high serum SLX level as an independent factor for worse outcome. In addition, logistic regression analysis revealed that a high serum SLX level was an independent predictor for liver metastasis. In conclusion, an elevated preoperative serum SLX level was a predictor for poor outcome after resection for gastric cancer, whereas CA19-9 was not.
Tohru Nakagoe, Kiyoyasu Fukushima, Terumitsu Sawai, Takashi Tsuji, Masaaki Jibiki, Atsushi Nakashima, Kenji Tanaka, Hiroyuki Yamaguchi, Toru Yasutake, Hiroyoshi Ayabe, Kokichi Arisawa and Hiroshi Ishikawa : Increased expression of sialyl Lewisx antigen as a prognostic factor in patients with stage 0, I and II gastric cancer., Cancer Letters, Vol.175, No.2, 213-221, 2002.
(要約)
Immunohistochemically detected expression of sialyl Lewis(x) (Le(x)) antigen was analyzed in 101 stage 0-II gastric cancers to clarify its prognostic value after curative gastrectomy. Patients with a high-expression of sialyl Le(x) antigen within their tumors had shorter disease-specific intervals than those with negative- or low-expressing tumors (P<0.0001). This difference was noted particularly in stage I-B or II disease. Multivariate Cox's regression analysis revealed sialyl Le(x) antigen expression to be an independent predictor of disease-specific survival (Hazard ratio=9.10). In conclusion, the increased expression of sialyl Le(x) antigen may serve as a prognostic factor after curative surgery for stages 0-II gastric cancer.
(キーワード)
Humans / Lewis Blood-Group System / Neoplasm Staging / Oligosaccharides / Prognosis / Stomach Neoplasms / Survival Rate / Time Factors
Hisayuki Hamada, Hiroshi Yatsuhashi, Koji Yano, Manabu Daikoku, Kokichi Arisawa, Osami Inoue, Michiaki Koga, Keisuke Nakata, Katsumi Eguchi and Michitami Yano : Impact of aging on the development of HCC in post-transfusion chronic hepatitis C., Cancer, Vol.95, No.2, 331-339, 2002.
(要約)
Hepatitis C virus (HCV) infection is a heterogeneous disease, the natural history of which remains controversial. There is solid evidence that chronic HCV infection is responsible for the occurrence of hepatocellular carcinoma (HCC). The aim of the current cohort study was to determine the rate of the development of HCC from the time of primary HCV infection and to assess the risk factors for the development of HCC in chronic posttransfusion hepatitis C patients. Four hundred sixty-nine patients with clinically compensated HCV, who had undergone a single blood transfusion comprised the current study cohort. Patients with other risk factors for chronic liver disease were excluded. All patients were referred to the liver center at the National Nagasaki Medical Center between December 1980 and December 1998 and were followed prospectively until the end of the analysis (June 2000). Follow-up data were obtained for 445 patients. The mean duration from HCV infection to the end of the observation was 28 years. Fifty-two patients (11.1%) progressed to HCC. The mean duration from the time of blood transfusion to the diagnosis of HCC was 31 years. Multivariate Cox regression analyses revealed age, fibrosis, duration from HCV infection to study entry, and alcohol consumption to be the independent factors affecting the development of HCC. The risk of developing HCC in patients age > or = 56 years was increased 7.8-fold compared with that in patients age < 56 years. The mean age of patients at the time of HCC diagnosis was 65 years (range, 58-79 years). At the time of diagnosis, 92% of the 52 HCC patients were age > 60 years and 38 of the HCC patients (73%) were in their 60s. There was a significantly negative correlation between the duration from HCV infection to the development of HCC and the age of the patient at the time of infection (correlation coefficient = 0.702; P < 0.0001; Y = 61.1-0.82X), indicating that the age of patients, rather than the duration of HCV infection, is more significant for HCC development in patients with posttransfusion HCV. Moreover, these data may contribute to the design of an optimal follow-up schedule for patients with posttransfusion HCV.
Kokichi Arisawa, Shigeru Katamine, Shimeru Kamihira, Kenji Kurokawa, Takashi Sawada, Midori Soda, Hiroshi Doi, Hiroshi Saito and Satoshi Shirahama : A nested case-control study of risk factors for adult T-cell leukemia/lymphoma among human T-cell lymphotropic virus type-I carriers in Japan., Cancer Causes & Control, Vol.13, No.7, 657-663, 2002.
(要約)
The purpose of this study was to investigate the serological risk factors for development of adult T-cell leukemia/lymphoma (ATL) among human T-cell lymphotropic virus type-I (HTLV-I) carriers. A nested case-control study was performed. The source population comprised 23,922 subjects who had either visited the outpatient clinic or who had received annual health check-ups at the K Hospital, Nagasaki, Japan, at least once during 1985-1996 (HTLV-I seroprevalence = 16.1%). Markers of HTLV-I infection were examined in stored sera from 29 incident cases of ATL diagnosed during 1985-1997, and 158 controls matched for sex, birth year, date of sample collection, and HTLV-I seropositivity (median follow-up = 6.4 years). In exact conditional logistic regression analysis, high levels of soluble interleukin-2 receptor (> or = 500 U/ml) and high HTLV-I antibody titers (> or = 1,024) were independently associated with an increased risk of developing ATL (Odds ratio 20.5. 95% confidence interval (CI) 4.5-194 and 2.9, 95% CI 0.98-9.5, respectively). The results remained essentially unchanged when the subjects were restricted to those whose histories were followed for two years or longer. These findings indicate that high soluble interleukin-2 receptor levels and high HTLV-I antibody titers are strong predictors of ATL among carriers of HTLV-I.
(キーワード)
Age Distribution / Carrier State / Case-Control Studies / Cohort Studies / Confidence Intervals / Female / HTLV-I Antibodies / Human T-lymphotropic virus 1 / Humans / Incidence / Japan / Leukemia-Lymphoma, Adult T-Cell / Logistic Models / Male / Odds Ratio / Probability / Prognosis / Reference Values / Risk Assessment / Risk Factors / Sex Distribution / Survival Analysis
Tohru Nakagoe, Kiyoyasu Fukushima, Terumitsu Sawai, Takashi Tsuji, Masaaki Jibiki, Atsushi Nakashima, Hiroyuki Yamaguchi, Toru Yasutake, Hiroyoshi Ayabe and Kokichi Arisawa : Evaluation of sialyl Lewisa, sialyl Lewisx and sialyl Tn antigens expression levels as predictors of recurrence after curative surgery in node-negative colorectal cancer patients., Journal of Experimental & Clinical Cancer Research, Vol.21, No.1, 107-113, 2002.
(要約)
This study aimed to determine whether sialyl Lewis(a) (Le(a)), sialyl Lewis(x )(Le(x)), or sialyl Tn antigen expression could identify a subset of node-negative colorectal cancer patients that are at high risk for recurrence after curative surgery. Tumor tissue samples from 90 patients with node-negative colorectal cancer, who had undergone surgical resection, were analyzed immunohistochemically for the expression of each antigen. Patients were classified as having low or high antigen expression depending on whether more or less than 40% of the field showed positive staining. The main outcome measure for each variable was disease-free interval. Sialyl Le(a), sialyl Le(x), and sialyl Tn antigens were expressed in 53 (58.9%), 41 (45.6%), and 34 (37.8%) carcinomas, respectively. The median follow-up was 83.5 months. Patients with high sialyl Le(x) expression had shorter disease-free intervals than those with low sialyl Le(x) expression (P = 0.0041); the expression of sialyl Le(a) or sialyl Tn antigens did not show a significant relationship with disease-free survival. Cox's regression analysis revealed that sialyl Le(x) expression was an independent predictor for disease-free survival, separate from T factor or tumor location. High sialyl Le(x) expression may be useful in identifying a subset of node-negative colorectal cancer patients who are at high risk for recurrence.
Tohru Nakagoe, Terumitsu Sawai, Takashi Tsuji, Masa-aki Jibiki, Atsushi Nakashima, Hiroyuki Yamaguchi, Toru Yasutake, Hiroyoshi Ayabe, Kokichi Arisawa and Hiroshi Ishikawa : Predictive factors for preoperative serum levels of sialyl Lewisx, sialyl Lewisa, and sialyl Tn antigens in gastric cancer patients., Anticancer Research, Vol.22, No.1A, 451-458, 2002.
(要約)
Preoperative serum levels of sialyl Lewis(a) (CA19-9), sialyl Lewis(x) (SLX) and sialyl Tn (STN) antigens in 180 patients with gastric cancer were examined to establish predictive factors for serum levels of these antigens compared with carcinoembryonic antigen (CEA). The patients were divided into low and high antigen groups. Multivariate logistic regression analysis revealed the following independent predictive factors for high antigen levels [odds ratio]: liver metastasis for CA19-9 [4.40], SLX [9.90], STN [39.65] and CEA [5.14]; peritoneal dissemination for SLX [4.78] or STN [13.01]; venous invasion for CEA [3.56]; lymph node metastasis for CA19-9 [4.51]. In addition, high CA19-9 levels were independently related to lymph node metastasis in patients with stage I or II tumors. In conclusion, high serum levels of CA19-9, SLX and STN are associated with liver metastasis, while high serum levels of SLX and STN are associated with peritoneal dissemination. In addition, high serum CA19-9 levels may represent an independent predictor for lymph node metastasis.
(キーワード)
Adult / Aged / Aged, 80 and over / Antigens, Tumor-Associated, Carbohydrate / CA-19-9 Antigen / Carcinoembryonic Antigen / Female / Gangliosides / Humans / Logistic Models / Male / Middle Aged / Oligosaccharides / Predictive Value of Tests / Preoperative Care / Stomach Neoplasms
(文献検索サイトへのリンク)
● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 12017332
Tohru Nakagoe, Terumitsu Sawai, Takashi Tsuji, Masaaki Jibiki, Masayuki Ohbatake, Atsushi Nakashima, Hiroyuki Yamaguchi, Toru Yasutake, Hiroyoshi Ayabe and Kokichi Arisawa : Prognostic value of serum sialyl Lea, sialyl Lex and sialyl Tn antigens in blood from the tumor drainage vein of colorectal cancer patients., Tumor Biology, Vol.22, No.2, 115-122, 2001.
164.
Tohru Nakagoe, Terumitsu Sawai, Takashi Tsuji, Masa-aki Jibiki, Masayuki Ohbatake, Atsushi Nakashima, Hiroyuki Yamaguchi, Nobuko Kurosaki, Toru Yasutake, Hiroyoshi Ayabe and Kokichi Arisawa : Increased serum level of sialyl Lewisx antigen in blood from the tumor drainage vein in patients with non-polypoid growth type of colorectal cancer., Journal of Experimental & Clinical Cancer Research, Vol.20, No.1, 85-90, 2001.
(要約)
Two types of colorectal cancer with distinct morphologies have been described in recent studies: polypoid growth type (PG-type) and non-polypoid growth type (NPG-type). We hypothesize that the morphologic differences may correspond to additional biological distinctions. Ratios of sialyl Lewisa (CA 19-9), sialyl Lewisx (SLX), or carcinoembryonic antigen (CEA) in the venous blood drainage from the tumor to that of the respective antigen in the peripheral venous blood (d/p ratio) was examined in order to ascertain whether or not the ratio is correlated with either the PG-type or NPG-type colorectal tumor growth pattern. Blood samples from 118 patients with colorectal cancer were obtained from a peripheral vein and from the tumor drainage vein during surgical excision of the tumor. Statistical tests were conducted by univariate and multivariate (logistic regression) analyses. Among the cancers examined there were 17 PG-type (14.4%) and 101 NPG-type (85.6%). NPG-type cancers had a higher frequency of moderately differentiated adenocarcinoma cells and T3/T4 tumors than PG-type cancers (P<0.0001 and P<0.0001, respectively). NPG-type cancers had a more advanced stage than PG-type cancers (P=0.0007). The d/p ratio of SLX in NPG-type cancers was significantly higher than that in PG-type cancers (P=0.028). Multivariate logistic regression analysis showed that three variables, namely histologic type, T factor, and d/p ratio of SLX, were independently related to tumor growth patterns. In conclusion, NPG-type cancers are characterized by a high SLX d/p ratio, which may be at least partly responsible for a different tumor progression pattern compared to other cancer types.
Kokichi Arisawa, Atsuhiro Nakano, Hiroshi Saito, Xiao-Jie Liu, Michiyo Yokoo, Midori Soda, Takashi Koba, Tatsuya Takahashi and Kenichiro Kinoshita : Mortality and cancer incidence among a population previously exposed to environmental cadmium., International Archives of Occupational and Environmental Health, Vol.74, No.4, 255-262, 2001.
Tohru Nakagoe, Terumitsu Sawai, Takashi Tsuji, Masa-aki Jibiki, Atsushi Nakashima, Hiroyuki Yamaguchi, Toru Yasutake, Nobuko Kurosaki, Hiroyoshi Ayabe and Kokichi Arisawa : Preoperative serum levels of sialyl Lewisa, sialyl Lewisx, and sialyl Tn antigens as prognostic markers after curative resection for colorectal cancer., Cancer Detection and Prevention, Vol.25, No.3, 299-308, 2001.
(要約)
In this study, we examined the preoperative serum levels of sialyl Lewisa, sialyl LewisX, sialyl Tn, and carcinoembryonic antigen in 243 colorectal cancer patients in order to clarify the role of these antigens as prognostic factors after curative surgery. The patients were divided into two groups: low and high antigen groups (lower and higher than a selected diagnostic-based cut-off value). Patients with high serum levels of sialyl Lewisa and carcinoembryonic antigen had shorter disease-free intervals than those with low serum levels of the respective antigen, although sialyl Lewisx and sialyl Tn showed no significant differences. Multivariate analysis revealed that three independent prognostic variables, including depth of tumor invasion, lymph node metastasis, and serum sialyl Lewisa level, did prove to have value in predicting disease-free interval. In conclusion, among the four antigens examined in this study, the preoperative serum level of sialyl Lewisa is the only independent prognostic variable for recurrence after curative resection of colorectal cancer.
Xiao-Jie Liu, Kokichi Arisawa, Atsuhiro Nakano, Hiroshi Saito, Tetsuya Takahashi and Akiko Kosaka : Significance of cadmium concentrations in blood and hair as an indicator of dose 15 years after the reduction of environmental exposure to cadmium., Toxicology Letters, Vol.123, No.2,3, 135-141, 2001.
(要約)
To evaluate the significance of cadmium (Cd) concentrations in blood (B-Cd) and hair (H-Cd) as an indicator of dose, a cross-sectional study was performed on 40 residents in a Cd-polluted area, Nagasaki Prefecture, Japan, in 1996. In the study area, soil replacement of Cd-polluted rice fields ended in 1981. B-Cd and H-Cd were significantly higher in the study population than in the control subjects. B-Cd was positively correlated with urinary Cd (U-Cd) (Spearman r=0.50, P=0.06 for males and r=0.72, P=0.0001 for females), while H-Cd was weakly or moderately correlated with U-Cd. After adjustment for gender using logistic regression analysis, log(B-Cd) and log(U-Cd), but not log(H-Cd), were significantly associated with the prevalence of increased urinary beta2-microglobulin (P for trend <0.05). These findings suggest that B-Cd is a good indicator of cumulative dose many years after the reduction of environmental exposure to Cd. H-Cd may be weakly or moderately correlated with body burden.
(キーワード)
Adult / Aged / Aged, 80 and over / Body Burden / Cadmium / Cross-Sectional Studies / Environmental Exposure / Environmental Monitoring / Female / Hair / Humans / Logistic Models / Male / Middle Aged / Predictive Value of Tests / Sex Factors / Time Factors / beta 2-Microglobulin
Tohru Nakagoe, Terumitsu Sawai, Takashi Tsuji, Hiroyoshi Ayabe, Takayuki Nakazaki, Hiroshi Ishikawa, Kazuhiko Hatano, Kenji Kajiwara, Kousei Miyashita, Toshikazu Matsuo, Tatsuhiko Nogawa and Kokichi Arisawa : Prognostic value of carcinoembryonic antigen (CEA) in tumor tissue of patients with colorectal cancer., Anticancer Research, Vol.21, No.4, 3031-3036, 2001.
(要約)
To establish the prognostic value of carcinoembryonic antigen (CEA) concentration in tumor tissue (T-CEA), normal colonic mucosa (N-CEA) and pre-operative serum (S-CEA), we studied 79 patients who underwent resections for colorectal cancer. The patients were separated into groups reflecting laboratory values lower or higher than a diagnostic value (S-CEA) or the median value of the entire population (T-CEA, N-CEA). A high S-CEA predicted for more advanced stage (p = 0.028), whereas no association was noted between stage and CEA concentration for T-CEA and N-CEA groups. The high S-CEA and T-CEA groups had a worse clinical outcome (p=0.0036 and p=0.024, respectively), while survival of high versus low N-CEA groups did not differ. By Cox's regression analysis, high T-CEA concentration was an independent variable for poor outcome (Hazard ratio, 3.15), while S-CEA and N-CEA were not. In conclusion, a high T-CEA concentration was the only independent predictor of poor outcome after resection for colorectal cancer.
Tohru Nakagoe, Terumitsu Sawai, Takashi Tsuji, Masaaki Jibiki, Atsushi Nakashima, Hiroyuki Yamaguchi, Toru Yasutake, Hiroyoshi Ayabe, Kokichi Arisawa and Hiroshi Ishikawa : Pre-operative serum levels of sialyl Tn antigen predict liver metastasis and poor prognosis in patients with gastric cancer., EJSO - European Journal of Surgical Oncology, Vol.27, No.8, 731-739, 2001.
(要約)
To clarify the prognostic value of preoperative serum levels of sialyl Tn antigen (STN) for survival of gastric cancer patients. Pre-operative serum levels of STN, sialyl Lewis(a)antigen (CA19-9) and carcinoembryonic antigen (CEA) were examined in 180 patients who underwent resection of gastric cancer. Patients were divided into high and low antigen groups on the basis of a selected diagnostic-based cut-off value. Correlation between high antigen serum levels, established clinicopathologic factors and prognosis was examined by univariate and multivariate analysis. Twenty-eight patients (15.6%) were classified as high STN; 37 (20.6%) as high CA19-9; and 33 (18.3%) as high CEA. The survival time of the high STN, CA19-9 or CEA group was shorter than that of the respective low-antigen group (P<0.0001, P=0.0008 or P=0.0002, respectively). Patients with stage III/IV tumours with high STN had a shorter survival time that those with low STN (P=0.0004). Cox's regression with multiple covariates showed that high serum STN is an independent factor predicting a worse outcome in gastric cancer patients. Multiple logistic regression analysis revealed that high serum STN is an independent predictor for the development of liver metastasis. Pre-operative high serum levels of STN predict both liver metastasis and poor prognosis after resection for gastric cancer.
Kokichi Arisawa, Midori Soda, Shinsuke Endo, Keji Kurokawa, Shigeru Katamine, Isao Shimokawa, Takashi Koba, Tatsuya Takahashi, Hiroshi Saito, Hiroshi Doi and Satoshi Shirahama : Evaluation of adult T-cell leukemia/lymphoma incidence and its impact on non-Hodgkin lymphoma incidence in southwestern Japan, International Journal of Cancer, Vol.85, No.3, 319-324, 2000.
(要約)
The incidence of adult T-cell leukemia/lymphoma (ATL) and its impact on that of total non-Hodgkin lymphoma (NHL) were evaluated in Nagasaki, an area in southwestern Japan where human T-cell lymphotropic virus type I (HTLV-I) is endemic. The first study area comprised 4 towns located on the K Islands, which had a population of 26,870 in 1990. The overall HTLV-I seroprevalence estimated from the serologic survey of 18,485 subjects was 16.2%. By using the data from the Nagasaki Prefectural Cancer Registry (NPCR) and reviewing clinical and laboratory information, we identified 40 cases of ATL and 35 cases of other NHL diagnosed between 1985 and 1995. The crude annual incidence of ATL among 100,000 HTLV-I carriers aged 30 or older was estimated at 137.7 for men and 57.4 for women, with a significant sex difference after adjustment for age (rate ratio = 2.50, 95% confidence interval 1.32-4.73). The cumulative risk from 30 to 79 years of age was estimated at approximately 6.6% for men and 2.1% for women. Among the entire population, ATL accounted for 51 to 59% of the total NHL incidence, showing the strong impact of HTLV-I infection. The second study area comprised the whole of Nagasaki Prefecture (total population in 1990 = 1.56 million). Between 1985 and 1995, 989 cases of ATL and 1,745 cases of other NHL were registered in the NPCR. The world age-standardized annual incidence rate of ATL per 100,000 persons aged 30 or older was estimated at 10.5 for men and 6.0 for women, which accounted for approximately 37 to 41% of the total NHL incidence.
(キーワード)
Adolescent / Adult / Age Distribution / Aged / Aged, 80 and over / Antibodies, Viral / Child / Child, Preschool / Female / Human T-lymphotropic virus 1 / Humans / Incidence / Infant / Japan / Leukemia, T-Cell / Lymphoma, Non-Hodgkin / Lymphoma, T-Cell / Male / Middle Aged / Prevalence / Risk / Sex Distribution
Tetsuya Takahashi, Steven L Simon, Klaus R Trott, Keisei Fujimori, Noriaki Nakashima, Kokichi Arisawa and Minouk J Shoemaker : A progress report of the Marshall Islands Nationwide Thyroid Study: an international cooperative scientific study, The Tohoku Journal of Experimental Medicine, Vol.187, No.4, 363-375, 1999.
(要約)
The objective of this report is to present a summary of progress of the Marshall Islands Nationwide Thyroid Study. As well known, the US atomic weapons testing program in the Pacific was conducted primarily between 1946 and 1958 in the Marshall Islands. The nuclear tests resulted in radioactive contamination of a number of atolls and resulted in exposure of Marshallese to undefined levels before our study. Little information has been paid to health consequences among residents of the nearly twenty inhibited atolls except for some information about nodular thyroid disease which was reported on by an US group. In a cooperative agreement with the Government of the Marshall Islands, between 1993 and 1997 we studied the prevalence of both thyroid nodules and thyroid cancer among 4766 Marshallese potentially exposed to radioiodines from bomb test fallout. That group represents more than 65% of the population at risk. We diagnosed 45 thyroid cancers and 1398 benign thyroid nodules. In addition, 23 study participants had been operated on prior to our study for thyroid cancer. Presently, we are developing a database of information to estimate radiation doses and planning a statistical analysis to determine if a dose-response relationship exists. These data will be important for the health promotion of exposed people all over the world including Hiroshima, Nagasaki, Semipalatinsk, Chernobyl and other locations. A timely completion is important for purpose of assisting Marshallese as well as to add the global understanding of radiation induced thyroid cancer.
Kokichi Arisawa, Midori Soda, Masazumi Akahoshi, Tatsuki Matsuo, Eiji Nakashima, Masao Tomonaga and Hiroshi Saito : Human T-lymphotropic virus type-I infection, antibody titers and cause-specific mortality among atomic-bomb survivors., Japanese Journal of Cancer Research (Cancer Science), Vol.89, No.8, 797-805, 1998.
174.
Yoichi Sawaji, Noriyuki Haneda, Seiji Yamaguchi, Yasuhisa Kajino, Kenji Kishida, Shiro Seto, Nakao Kohishi, Kenji Waki, Kiyoshi Baba, Kokichi Arisawa, Tetsuro Kamiya and Chuzo Mori : Coronary risk factors in acute Kawasaki disease: correlation of serum immunoglobulin levels with coronary complications, Acta Pediatrica Japonica, Vol.40, No.3, 218-225, 1998.
175.
Kokichi Arisawa, Atsuhiro Nakano, Sumihisa Honda and Hiroshi Saito : Reproducibility of urinary beta-2 microglobulin and cadmium excretion among residents in a cadmium-polluted are during a 3-year period., Toxicology Letters, Vol.91, No.1,2, 147-152, 1997.
176.
Katsumi Eguchi, Tomoki Origuchi, Hiroyuki Takashima, Kokichi Iwata, Sigeru Katamine and Shigenobu Nagataki : High seropveralence of anti-HTLV-I antibody in rheumatoid arthritis, Arthritis and Rheumatism, Vol.39, No.3, 463-466, 1996.
Kaoru Terada, Shigeru Katamine, Katsumi Eguchi, Ryozo Moriuchi, Masako Kita, Hironori Shimada, Izumi Yamashita, Kokichi Iwata, Yoshiro Tsuji, Shigenobu Nagataki and Tsutomu Miyamoto : Prevalence of serum and salivary antibodies to HTLV-1 in Sjögren's syndrome., The Lancet, Vol.344, No.8930, 1116-1119, 1994.
179.
Kokichi Iwata, Shin-ichiro Ito, Hiroshi Saito, Mizuko Ito, Masazumi Nagatomo, Tomihiro Yamazaki, Shigeyuki Yoshida, Hisatsugu Suto and Kazuo Tajima : Mortality among inhabitants of an HTLV-I endemic area in Japan., Japanese Journal of Cancer Research (Cancer Science), Vol.85, No.3, 231-237, 1994.
180.
Kokichi Iwata, Hiroshi Saito, Masaki Moriyama and Atsuhiro Nakano : Renal tubular function after reduction of environmental cadmium exposure: a ten-year follow-up., Archives of Environmental Health, Vol.48, No.3, 157-163, 1993.
181.
Kokichi Iwata, Hiroshi Saito, Masaki Moriyama and Atsuhiro Nakano : Follow up study of renal tubular dysfunction and mortality in residents of an area polluted with cadmium., British Journal of Industrial Medicine (Occupational and Environmental Medicine), Vol.49, No.10, 736-737, 1992.
182.
Minoru Kasuya, Hidetoyo Teranishi, Keiko Aoshima, Terutaka Katoh, Hyogo Horiguchi, Yuko Morikawa, Muneko Nishijo and Kokichi Iwata : Water pollution by cadmium and the onset of Itai-itai disease, Water Science and Technology, Vol.25, No.11, 149-156, 1992.
183.
Kokichi Iwata, Hiroshi Saito and Atsuhiro Nakano : Association between cadmium-induced renal dysfunction and mortality: further evidence., The Tohoku Journal of Experimental Medicine, Vol.164, No.4, 319-330, 1991.
(要約)
Our previous follow-up study, carried out from 1979 to 1989, on 256 residents of Sasu, a cadmium (Cd)-polluted area located on Tsushima Island, Nagasaki Prefecture, Japan, showed a significant relationship between urinary beta 2-microglobulin (beta 2-m) excretion and mortality in men. To investigate the association between Cd-induced renal dysfunction and mortality more precisely, 275 residents in the same area aged 40-92 years, who had participated in a health survey conducted in May 1982, were followed to February 1989. The expected number of deaths was calculated on the basis of the sex- and 5-year-age-specific mortality rates for Tsushima Island in 1985. In both men and women with urinary beta 2-m concentrations greater than 1,000 micrograms/g creatinine, observed deaths were greater than the expected. However, the P value of the difference was less than 0.05 only in women. Analysis by the Cox proportional hazards model showed that, in both men and women, serum beta 2-m and creatinine, as well as urinary total protein and beta 2-m were significantly or marginally significantly related to mortality independent of age. In men, serum beta 2-m was more strongly related to mortality than urinary beta 2-m. The results provide further evidence for the causal association between Cd-induced renal dysfunction and mortality. The present report also discusses the role played by decreased glomerular filtration rate in the excess mortality of subjects with Cd-induced renal dysfunction.
(キーワード)
Adult / Age Factors / Aged / Aged, 80 and over / Biological Markers / Biometry / Cadmium Poisoning / Creatinine / Environmental Pollution / Female / Humans / 日本 (Japan) / Kidney Diseases / Male / Middle Aged / Sex Characteristics / beta 2-Microglobulin
Kokichi Iwata, Hiroshi Saito, Masaki Moriyama and Atsuhiro Nakano : Association between renal tubular dysfunction and mortality among residents in a cadmium-polluted area, Nagasaki, Japan., The Tohoku Journal of Experimental Medicine, Vol.164, No.2, 93-102, 1991.
(要約)
A retrospective cohort study was carried out to clarify the effect of exposure to environmental cadmium (Cd) on mortality. A total of 256 residents aged 50 years or older, living in Sasu, a Cd-polluted area in Tsushima Island in Nagasaki Prefecture, Japan, were followed from July 1979 to February 1989. The expected number of deaths calculated was based on the sex- and age- specific mortality rate in Tsushima Island in 1985. In Sasu residents of both sexes with urinary beta 2-microglobulin (beta 2-m) concentration greater than 1,000 microgram/g creatinine in 1979, observed deaths were greater than expected. However, the p value of the difference was less than 0.05 only in men. The relationships of age, mean blood pressure, urinary beta 2-m and urinary Cd concentration to mortality were examined using Cox's proportional hazards model. Urinary beta 2-m was independently and significantly related to mortality in men but not in women. The results suggest an association between Cd-induced renal tubular dysfunction and mortality.
Masaki Moriyama, Sin-ichi Matsubara, Hiroshi Saito and Kokichi Iwata : Community people's preference of hand drawn face graph as a health informing device, The Tohoku Journal of Experimental Medicine, Vol.160, No.1, 37-46, 1990.
(要約)
Although the cartoon of a face is an effective device to visualize the image of numerical indices, its use is not popular among community health personnel. In the present study, we used the face graph as an aid for health informing and educating activities in the setting of a community health activity. For this purpose, we designed a special sheet to draw face by hand. By using this sheet, each person can draw his/her 'face' from one's laboratory data index under the guidance of additional lines. The acceptability of this hand drawn face was evaluated by 283 people aged 65 years and over at a health counseling session. For both men and women, a higher percentage preferred face (37% for men, 40% for women) over numeral (23% for men, 17% for women). The preference for the face graph was also observed at each of three age groups within each sex. The highest affinity to face (64%) was observed for the 14 women who reported as cataract patients.
(キーワード)
Aged / Aged, 80 and over / Female / Health Education / Humans / 日本 (Japan) / Male / Medical Illustration / Middle Aged
Kokichi Iwata, Terutaka Katoh, Yuko Morikawa, Keiko Aoshima, Muneko Nishijo, Hidetoyo Teranishi and Minoru Kasuya : Urinary trehalase activity as an indicator of kidney injury due to environmental cadmium exposure., Archives of Toxicology, Vol.62, No.6, 435-439, 1988.
学術レター:
1.
Kokichi Arisawa, Midori Soda, Masahito Ono, Hirokazu Uemura, Mineyoshi Hiyoshi and Akihiko Suyama : Trends of incidence rate of adult T-cell leukemia/lymphoma in an HTLV-1 endemic area in Japan, International Journal of Cancer, Vol.125, No.3, 737-738, 2009.
(キーワード)
Adult / Age Distribution / Aged / Aged, 80 and over / Endemic Diseases / Female / HTLV-I Infections / Humans / Incidence / Japan / Leukemia-Lymphoma, Adult T-Cell / Male / Middle Aged / Odds Ratio / Registries / Risk Assessment / Risk Factors / Time Factors
Hiroshi Saito, Kokichi Iwata and Masaki Moriyama : Mortality rate among cadmium-exposed inhabitants was significantly higher than entire Japanese population., Archives of Environmental Health, Vol.51, No.6, 471-473, 1996.
The research interest of authors has focused on the risk assessment of environmental pollutantssuch as cadmium and dioxin-related compounds, and epidemiology of human T-cell lymphotropicvirus type-I(HTLV-I)infection. The authors(1)showed that low-molecular weight proteinuriaand reduced glomerular filtration rate caused by environmental cadmium were strongly associatedwith shortened survival，(2)clarified serological risk factors for development of adult T-cellleukemia/lymphoma among asymptomatic HTLV-I carriers(plasma levels of soluble interleukin2-receptor>＝500U/ml and HTLV-I antibody titer>＝1，024)，(3)conducted the first prospectivestudy of HTLV-I infection and development of malignances other than ATL, and found a significantlyreduced risk of gastric cancer among HTLV-I carriers, and(4)by a cooperative study, clarified anew pathogenicity of HTLV-I(association with Sj¨ogren's syndrome)
Naoko Matsui, Tanaka Keiko, Yamamoto Yohei, Saika Reiko, Iizuka Takahiro, Matsui Makoto, Kokichi Arisawa, Ryuji Kaji, Kuwabara Satoshi and Yuishin Izumi : Prevalence, clinical profiles, and prognosis of Stiff-person syndrome in Japanese nationwide survey, The 9th Congress of the European Academy of Neurology (EAN), Jul. 2023.
2.
Nguyen Van Tien, Kokichi Arisawa, Sakurako Kamano, Takeshi Watanabe and Masashi Ishizu : Association of metabolic syndrome and metabolically unhealthy obesity with cancer mortality, Asia Pacific Conference 2022, Beppu, Dec. 2022.
3.
Tirani Bahari, Hirokazu Uemura, Sakurako Kamano, Miwa Yamaguchi, Mariko Nakamoto, Masashi Ishizu, Miho Fujioka and Kokichi Arisawa : Adherence to the Japanese Food Guide Spinning Top and Prevalence of Metabolic Syndrome and Its Components, 2017 International Congress of Diabetes & Metabolism, Seoul, Koria, Sep. 2017.
4.
Tomohiko Isobe, Miyuki Iwai-Shimada, Murzembobasilua Andre, Sachiko Tsukahara, Junya Kasamatsu, Kokichi Arisawa and Shoji F Nakayama : Biomonitoring of dioxins and other chemicals in Japan: Summary of a nation-wide survey during 2011-2016, Dioxin 2017, Vancouver, Aug. 2017.
5.
Kokichi Arisawa, Y Nagai, A Harita, Y Chisaki, M Hijiya and T Matsumura : The survey of the exposure to dioxins and other chemical compounds in humans, DIOXIN2016, Firenze, Italy, Aug. 2016.
6.
Bahari Tirani, Hirokazu Uemura, Sakurako Katsuura-Kamano, Miwa Yamaguchi, Mariko Nakamoto, Miki Keisuke, Sawachika Fusakazu and Kokichi Arisawa : Bread and Dairy Pattern is Associated with Increased Adiponectin Concentration among Japanese Adults., Vancouver, Canada, Dec. 2015.
7.
Sakurako Kamano, Hirokazu Uemura, Miwa Yamaguchi, Sawachika Fusakazu, Tirani Bahari, Miki Keisuke, Kokichi Arisawa and J-MICC Study Group : An appetite-related gene, MC4R polymorphism is associated with serum triglyceride levels in the general Japanese population- the J-MICC Study, International Symposium on Dietary Antioxidants and Oxidative Stress in Health 2015, Awaji, Aug. 2015.
8.
Kokichi Arisawa, Yoshie Nagai, Atsushi Harita, Yoichi Chisaki, Masaki Hijiya and Tohru Matsumura : The survey of the exposure to dioxins and other chemical compounds in humans, 34th International Symposium on Halogenated Persistent Pollutants, Madrid, Spain, Madrid, Sep. 2014.
9.
Miwa Yamaguchi, Hirokazu Uemura, Sakurako Kamano, Hidenobu Takami, Fusakazu Sawachika, Mariko Nakamoto, Tomoya Juta and Kokichi Arisawa : Dietary habits may be associated with sleep-wake rhythm disorders., 16th International Congress of Dietetics., Sydney, Sep. 2012.
10.
Midori Soda, Masako Iwanaga, Yasushi Miyazaki, Yasuaki Yamada, Kokichi Arisawa, Ichiro Sekine and Akihiko Suyama : Trend of ATL/ATLL Incidence in an HTLV-1 endemic area in Nagasaki, Japan, The 31st Annual Meeting of Iinternational Association of Cancer Registries, New Orleans, Jun. 2009.
11.
Hirokazu Uemura, Kokichi Arisawa, H Sato, Y Sumiyoshi, K Morinaga, K Kodama, T Suzuki, M Nagai and T Suzuki : Associations of low levels exposure to dioxins with prevalent diabetes in Japanese general population, DIOXIN 2007 International Symposium, Tokyo, Sep. 2007.
12.
M Hasegawa, T Kitamado, H Fujii, A Iguchi, Kokichi Arisawa, Hirokazu Uemura, Y Chisaki, M Hijiya, T Matsumura and T Suzuki : The survey on the accumulation of dioxins in humans - dioxin concentration of general environmental inhabitants in Japan and intake survey through diet, Dioxin 2007 International Symposium, Tokyo, Sep. 2007.
13.
Kokichi Arisawa, Hirokazu Uemura, H Sato, Y Sumiyoshi, K Morinaga, K Kodama, T Suzuki, M Nagai and T Suzuki : Dietary intake of dioxins among Japanese population estimated by duplicate portion analysis: low proportion of adults whose long-term intake exceeded the tolerable daily intake, Dioxin 2007 International Symposium, Tokyo, Sep. 2007.
14.
Hirokazu Uemura, Toshiyuki Yasui, Y Miyatani, M Yamada, Mineyoshi Hiyoshi, Hideo Takeda, Kokichi Arisawa and Minoru Irahara : Relationships between circulating osteoprotegerin and the risk factors of vascular disorders in postmenopausal women., The 3rd Scientific Meeting of the Asian Pacific Menopause Federation (APMF), Taipei, Mar. 2007.
15.
Mineyoshi Hiyoshi, Hirokazu Uemura, Hideo Takeda, Hiroshi Kido and Kokichi Arisawa : Quantitative proteomic analysis of testes in treated and untreated mice with bisphenol A by MALDI-TOF/TOF, 20th IUBMB International Congress of Biochemistry and Molecular Biology and 11th FAOBMB Congress, Kyoto, Jun. 2006.
釜野 桜子, 有澤 孝吉, 石津 将, 渡邊 毅, Nguyen Van Tien, for the J-MICC Study Group : 朝食欠食および睡眠時間とメタボリック症候群との関連:J-MICC Study, 第264回徳島医学会学術集会, 2022年2月.
5.
Tien Van Nguyen, Kokichi Arisawa, Sakurako Kamano, Takeshi Watanabe, Masashi Ishizu and for the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study Group : Associations of metabolic syndrome and metabolically unhealthy obesity with cancer mortality: Results of prospective cohort study in Japanese population, 第264回徳島医学会学術集会, Feb. 2022.
Tien Van Nguyen, Kokichi Arisawa, Sakurako Katsuura-Kamano, Takeshi Watanabe, Masashi Ishizu and for the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study Group : Associations of metabolic syndrome and metabolically unhealthy obesity with cancer mortality, 第32回日本疫学会学術総会, Jan. 2022.
8.
釜野 桜子, 有澤 孝吉, 石津 将, 渡邊 毅, NGUYEN TIEN VAN, for the J-MICC Study Group : 大豆製品およびイソフラボン摂取量と全死亡・がん死亡との関連:J-MICC Study, 第32回日本疫学会学術総会, 2022年1月.
釜野 桜子, 有澤 孝吉, NGUYEN TIEN VAN, 上村 浩一, Group the J-MICC Study for : 朝食欠食および睡眠時間とメタボリック症候群との関連:J-MICC Study, 第31回日本疫学会学術総会, 2021年1月.
11.
Tien Van Nguyen, Kokichi Arisawa, Hirokazu Uemura and Sakurako Katsuura-Kamano : Association between nutrient patterns and fatty liver index: Baseline survey of the Japan Multi-Institutional Collaborative Cohort Study in Tokushima, Japan, 第31回日本疫学会学術総会, Jan. 2021.
12.
有澤 孝吉, 勝浦-釜野 桜子, NGUYEN TIEN VAN, 上村 浩一, Group J-MICC Study the : 食事酸負荷とメタボリック症候群との関連:J-MICC Study, 第31回日本疫学会学術総会, 2021年1月.
13.
上村 浩一, 釜野 桜子, NGUYEN TIEN VAN, 有澤 孝吉 : 労働者における脂肪肝の簡易指標である Fatty Liver Index と慢性炎症や動脈スティフネスとの関連: J-MICC Study 徳島地区調査より, 第63回中国四国合同産業衛生学会, 2019年12月.
Hanada Kenta, Naoko Matsui, Hiroyuki Nodera, Kuzume Daisuke, Kenta Sato, Iwasa Naoki, Unai Yuki, Saka Waka, Yoshimichi Miyazaki, Yamazaki Hiroki, Yusuke Osaki, Takahiro Furukawa, Yamasaki Masahiro, Yuishin Izumi, Kusunoki Susumu, Kokichi Arisawa and Ryuji Kaji : Guillain-Barre syndrome in a local area in Japan, 2006-2015: An epidemiological and clinical study of 108 patients, XX World Congress of Neurology, Sep. 2017.
25.
Hirokazu Ogino, Masaki Hanibuchi, Souji Kakiuchi, Atsuro Saijo, Toshifumi Tezuka, Yuko Toyoda, Satoshi Sakaguchi, Hisatsugu Goto, Kokichi Arisawa and Yasuhiko Nishioka : Analysis of the Prognostic Factors of Extensive Disease Small-Cell Lung Cancer Patients in Tokushima University Hospital., The 57th Annual Meeting of the Japanese Respiratory Society, Apr. 2017.
Tirani Bahari, Hirokazu Uemura, Sakurako Kamano, Miwa Yamaguchi, Mariko Nakamoto, Mineyoshi Hiyoshi and Kokichi Arisawa : The Association between Dietary Pattern and Serum Adiponectin: A Cross Sectional Study In Japanese Population, 第25回日本疫学会学術総会, Jan. 2015.