Profile of participants and genotype distributions of 108 polymorphisms in a cross-sectional study of associations of genotypes with lifestyle and clinical factors: a project in the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Values of cardio-ankle vascular index (CAVI) between Amami islands and Kagoshima mainland among health checkup examinees.

AIM: To investigate the prevalence and geographical variation of high arterial stiffness in groups from the Amami islands (Amami) and Kagoshima mainland (mainland), Japan, using the cardio-ankle vascular index (CAVI) as a surrogate marker of arterial stiffness. METHODS: We recruited 4,523 health checkup examinees from Amami and 440 examinees from the mainland, with an age range of 40-69 years. The frequency of high arterial stiffness (CAVI≥9.0) was geographically compared between the regions, and both mean CAVI values were compared with those of the healthy Japanese population with less risk factors for coronary artery disease. Clinical, lifestyle, and regional factors for increased CAVI values were estimated by the multiple linear regression model. RESULTS: The frequency of high arterial stiffness on Amami was significantly lower than on the mainland. Mean CAVI values on Amami were similar in males and lower in females than in the healthy Japanese population, but those on the mainland were higher for both sexes. Age, systolic blood pressure, triglycerides, fasting blood glucose, and a history of hypertension and diabetes mellitus were positively related to increased CAVI values on Amami. The regional factor of Amami, compared with the mainland, was negatively related to increased CAVI values in both sexes after adjusting for traditional cardiovascular risk factors. CONCLUSION: CAVI values in Amami residents were significantly lower than in mainland residents, suggesting that environmental or genetic factors might have improved arterial stiffness in the Amami population.

Gene variants in PPARD and PPARGC1A are associated with timing of natural menopause in the general Japanese population.

OBJECTIVES: 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. STUDY DESIGN: 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. MAIN OUTCOME MEASURES: 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. RESULTS: 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. CONCLUSIONS: 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.