Effect of smoking and obesity on the association between HMGCR rs12654264 and type 2 diabetes in a Korean population

Methods A total of 4,239 participants were included. Fasting blood glucose (FBG) and lipid levels were measured after a 12-hour fast. Diabetes was defined as FBG ≥ 126 mg/dL, a prior diagnosis of diabetes, or use of antidiabetic medication. Associations were evaluated using linear regression under an additive genetic model and logistic regression under a recessive model. Interaction terms were included to assess effect modification by smoking and waist circumference. Results The rs12654264 SNP was associated with FBG and LDL-C levels. After adjustment for age, sex, and BMI, healthy men with the TA/AA genotype had an increased risk of diabetes compared with those with the TT genotype (OR 1.50; 95% CI 0.98–2.29). The association was stronger among male non-smokers and light smokers (OR 3.59; 95% CI 1.37–9.39; p = 0.0094) than among heavy or former smokers. The interaction between rs12654264 and smoking was significant (P for interaction = 0.0141). A stronger association was also observed in men with waist circumference < 86 cm (OR 9.12; 95% CI 1.21–68.6). Conclusions The HMGCR rs12654264 variant was associated with type 2 diabetes in Korean men. This association was stronger among lean individuals and non-smokers or light smokers, suggesting potential gene–environment interaction.