Associations between hOGG1 Ser326Cys polymorphism and increased body mass index and fasting glucose level in the Japanese general population

Background: Evidence suggests that Ser326Cys, a genetic polymorphism of human 8-oxoguanine glycosylase 1 (hOGG1), is associated with insulin resistance and type 2 diabetes; however, the underlying mechanism is unclear. Recently, an animal study showed a significant association between the hOGG1 genotype and obesity, although evidence for such an association in humans is limited. The purpose of this study was to examine the association between the hOGG1 genotype and body mass index (BMI) and fasting blood glucose (FBG) levels. Methods: Cross-sectional analysis was conducted using the baseline survey data from a Japan Multi-Institutional Collaborative Cohort Study, which included 1793 participants aged 40-69 years. The hOGG1 polymorphism was detected using a multiplex polymerase chain reaction-based invader assay. Multiple linear regression, analysis of covariance, and logistic regression were used to control for confounding variables. Results: The Cys allele was significantly associated with increased BMI, FBG level, and total cholesterol (TC) level, even after adjustment for gender, age, energy intake, alcohol, smoking, physical activity, and family history of diabetes. An association with BMI was still observed after further adjustment for FBG and TC, but not for the study area (Amami or the mainland). The Cys/Cys genotype was significantly more prevalent in the participants with higher BMI (>27.5 kg/m²). However, the impact of genotype decreased and significance disappeared after adjusting for the study area. Conclusions: The present results suggest that the study area being inside Japan confounds the association between hOGG1 genotype and obesity.