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Glutathione peroxidase 1 Pro198Leu variant contributes to the metabolic syndrome in men in a large Japanese cohort^1,2,3

¹ From the Department of Geriatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan (MK and AI), and the Department of Epidemiology, National Institute for Longevity Sciences, Obu, Aichi, Japan (FA and HS)

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/TT genotypes had significantly higher waist-hip ratios, triacylglycerol concentrations, homeostasis model assessment for β-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/TT genotypes 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.