The Pro12Ala polymorphism of the PPAR-γ2 gene affects associations of fish intake and marine n-3 fatty acids with glucose metabolism

Background/Objectives: Data on associations between marine n-3 fatty acids and glucose metabolism are inconsistent. Therefore, we explored effects of the Pro12Ala polymorphism in peroxisome proliferator-activated receptor (PPAR)-gamma 2 gene on associations of fish intake and dietary and plasma eicosapentaenoic and docosahexaenoic acid with glucose metabolism. The design comprises of the cross-sectional analysis. Subjects/Methods: The Pro12Ala variant in the PPAR-gamma 2 (PPARG) gene was genotyped in 571 non-diabetic relatives of subjects with type II diabetes. The dietary intake was measured by a 3-day food record, and the plasma cholesterol ester fatty acid composition was analysed with gas chromatography. Associations of dietary and plasma variables with insulin resistance and fasting and 2-h glucose and free fatty acid concentrations were analysed with multiple linear regression analysis. Results: In men, there was a significant interaction between PPARG polymorphism and plasma docosahexaenoic acid on fasting free fatty acid concentration (P = 0.036), and genotype-stratified models showed an inverse association in Pro homozygotes only (P = 0.028). In women, the proportion of plasma eicosapentaenoic acid was higher in Ala-allele carriers compared to Pro homozygotes (1.67 vs 1.44% respectively, P = 0.006). A significant interaction between PPARG polymorphism and fish intake on 2-h glucose was found in women (P = 0.021), and genotype-stratified models suggested an inverse association in Ala-allele carriers only (P = 0.039). Conclusions: The findings suggest that PPARG polymorphism might affect the plasma proportion of eicosapentaenoic acid and modulate the associations of fish intake and marine n-3 fatty acids with glucose metabolism and fasting free fatty acids.