Modulation of the Association between the PEPD Variant and the Risk of Type 2 Diabetes by n-3 Fatty Acids in Chinese Hans

Abstract

Background/Aims: Type 2 diabetes (T2D) is modulated by the interactions between genetic and dietary factors. This study sought to examine whether the associations of genome-wide association study (GWAS)-identified genetic variants with T2D risk were modulated by n-3 fatty acids in Chinese Hans. Methods: Six hundred and twenty-two T2D patients and 293 healthy controls were recruited. Erythrocyte phospholipid fatty acids were measured by standard methods. Nine GWAS-identified T2D-related single-nucleotide polymorphisms (SNPs) were genotyped. These SNPs were all identified in GWAS of Asian populations with a high minor allele frequency (>0.2). Results: Among the 9 SNPs, only rs3786897 at PEPD (peptidase D) showed a significant interaction with n-3 fatty acids (p_interaction after Bonferroni correction = 0.027). The rs3786897 A allele was associated with a higher risk of T2D [GA+AA vs. GG: odds ratio (OR) = 2.16, 95% confidence interval (CI) 1.32-3.55] when n-3 fatty acids were lower than the population median, but no significant association (GA+AA vs. GG: OR = 0.63, 95% CI 0.35-1.12) was observed when n-3 fatty acids were higher than the median. Conclusions: The association between the PEPD genetic variant and the risk of T2D was modulated by n-3 fatty acids. Higher n-3 fatty acids may abolish the adverse effect of the risk allele at PEPD for T2D.