The relation between type 2 diabetes and gene-gene interactions of peroxisome proliferator-activated receptors for non-Hypertriglyceridemic waist and Hypertriglyceridemic waist populations

Abstract

Objective: Recent researches have shown that the Hypertriglyceridemic waist (HTGW) was the high risk factors of diabetes and cardiovascular disease, also, it may plays a key role in modulating genetic predispositions to type 2 diabetes (T2DM).This study aims to test the hypothesis that lipid metabolism-related genes (PPARs) may contribute to the cause of T2DM in an individual and/or interactive way among the HTGW and non-HTGW groups. Method: We randomly selected 820 subjects for genetic polymorphism research based on the cohort study of metabolic syndrome (MS) in Jiangsu province China. The HTGW was defined as a waist circumference of 85cm or more in men, and a waist circumference of 80cm or more in women, and a triglyceride level of 1.70 mmol/L or more; Select 10 single nucleotide polymorphisms (SNPs) of the three subtypes of PPARs for polymorphism testing, in which the SNP(rs4253778) was analyzed by using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method, the remaining SNPs was analyzed by using the Taqman fluorescent probe; Applying logistic regression to analyze the relations between gene polymorphism and T2DM;Utilizing Generalized multifactor dimensionality reduction(GMDR)method to analyze the gene-gene interactions. Result: Single-locus of the Logistic regression analysis indicated that, both SNP (rs3856806) of the non-HTGW group and SNP (rs2016520) of HTGW group was closely related to the risk of T2DM [OR and 95% CI were 0.16 (0.04-0.57) and 0.11 (0.01-0.94)]. In addition, Having been adjusted by the covariates such as gender, age, smoking, alcohol consumption, high-fat diet, low-fiber diet, occupational physical activities and so on, Gene-gene interactions of GMDR model demonstrated that interactions between two SNPs (rs1800206 and rs3856806) were distinct among the non-HTGW population (P = 0.0107); and that interactions among the three SNPs (rs2016520, rs4684847 and rs709158) were obvious among the HTGW population (P = 0.0107). Conclusion: The results suggest that the SNPs from the PPARs genes may contribute to the risk of T2DM individually and/or interactively, with or without HTGW.