Introduction The peroxisome proliferator-activated receptor-γ2(PPARG2) Pro12Ala gene variant has been consistently associated with diabetes mellitus (DM). However, interactions between this polymorphism and lifestyle factors on DM remain poorly understood. The purpose of this study was to examine if carrying Ala allele was inversely associated with haemoglobin A1c (HbA1c) levels with any such interactions.

Methods We made a cross-sectional analysis using the data from the baseline survey of the Japan Multi-institutional Collaborative Cohort Study. After excluding 1882 participants who had medication for DM, dietary energy intake >4000 kcal/day, and/or any missing data on PPARG2 polymorphism or HbA1c, 1281 men and 1356 women aged 40–69 were analysed. PPARG2 polymorphism was determined by multiplex PCR-based invader assay. BMI and fat/energy intake were categorised into four levels. Multiple linear regression analysis and analysis of covariance were used to control for confounding variables (age, BMI, fat/energy intake, alcohol, smoking, and physical activity) and to examine possible interactions.

Results After adjustment for the above covariates, Ala allele was significantly inversely associated with HbA1c in women, but not in men. This inverse association in women was evident in the highest level of BMI or fat/energy intake. Contrarily, in men, a significant positive association between Ala allele and HbA1c was observed in the highest level of fat/energy.

Conclusion These results indicate that the association between PPARG2 Pro12Ala polymorphism and HbA1c may be modified by gender, obesity, and high fat diet. This study was conducted for J-MICC Study Group.