PPARGC1A rs3736265 G>A polymorphism is associated with decreased risk of type 2 diabetes mellitus and fasting plasma glucose level

Abstract

It has been reported that peroxisome proliferator-activated receptor gamma (PPARG) and peroxisome proliferator-activated receptor gamma co-activator 1 (PPARGC1) family (e.g. PPARGC1A and PPARGC1B) are key agents in the development and pathophysiology of type 2 diabetes mellitus (T2DM). In this study, we designed a case-control study and selected PPARG rs1801282 C>G, PPARG rs3856806 C>T, PPARGC1A rs8192678 C>T, PPARGC1A rs2970847 C>T, PPARGC1A rs3736265 G>A, PPARGC1B rs7732671 G>C and PPARGC1B rs17572019 G>A polymorphisms to assess the relationship between these polymorphisms and T2DM using the SNPscan method. A total of 502 T2DM patients and 784 non-diabetic controls were enrolled. We found that PPARGC1A rs3736265 G>A polymorphism was correlated with a borderline decreased susceptibility of T2DM. In a subgroup analysis by age, sex, alcohol use, smoking status and body mass index, a significantly decreased risk of T2DM in <65 years and female groups was found. Haplotype comparison analysis indicated that CTTCGGG and CTCTGGG haplotypes with the order of PPARG rs1801282 C>G, PPARG rs3856806 C>T, PPARGC1A rs8192678 C>T, PPARGC1A rs2970847 C>T, PPARGC1A rs3736265 G>A, PPARGC1B rs7732671 G>C and PPARGC1B rs17572019 G>A polymorphisms in gene position significantly increased the risk of T2DM. However, CCCCACA haplotype conferred a decreased risk to T2DM. We also found that PPARGC1A rs3736265 A allele decreased the level of fasting plasma glucose (FPG), while increased the level of Triglyceride. In conclusion, Our findings suggest that variants of PPARGC1A rs3736265 G>A polymorphism decrease the level of FPG, improving the expectation of study in individual's prevention strategies to T2DM.