Glutathione peroxidase 1 Pro198Leu variant contributes to the metabolic syndrome in men in a large Japanese cohort

Background: There has been much interest in the role of free radicals and oxidative stress in the pathogenesis of metabolic syndrome (MetS). Cellular antioxidant enzymes such as glutathione peroxidase 1(GPX1) play a central role in the control of reactive oxygen species. Objective: We examined whether GPX1 polymorphism (Pro198Leu) is associated with MetS as well as with each component of MetS. Design: The study was a cross-sectional analysis of randomly selected, community-dwelling Japanese persons aged 40-70 y (1128 M, 1105 F). Results: The genotype frequencies for the GPX1 Pro198Leu polymorphism in this cohort were 0.846, 0.151, and 0.003 for CC, CT, and TT, respectively. The CT/TTgenotypes had significantly higher waist-hip ratios, triacylglycerol concentrations, homeostasis model assessment for P-cell function, and systolic and diastolic blood pressures in men (P = 0.045, 0.012, 0.011, 0.004, and 0.003, respectively) than did the CC genotype; the CC/TT genotypes also had higher insulin in both sexes (P = 0.019 for men, P = 0.010 for women) and higher body fat mass (P = 0.027) and homeostasis model assessment for insulin resistance (P = 0.008) in women. The CT/TT genotypes showed significant association with higher prevalence of MetS as defined by 2 commonly used criteria in men [odds ratio (OR): 2.02; 95% CI: 1.30, 3.15 by the International Diabetes Federation criteria; OR: 1.49; 95% CI: 1.02, 2.18 by the modified National Cholesterol Education Program criteria) but not in women. The CT/TTgenotypes showed a higher prevalence of central obesity (OR: 1.93; 95% CI: 1.31, 2.85) and hypertriglyceridemia (OR: 1.52; 95% CI: 1.08, 2.15) in men but not in women; there were no differences in other components of MetS between the CC and CT/TT genotypes in either sex. Conclusion: GPX1 Pro198Leu variants are associated with the prevalence of MetS in Japanese men but not in women.