The Association Between PPARγgene Polymorphisms And Non-alcoholic Fatty Liver Disease

Objective:Nonalcoholic fatty liver disease (NAFLD) is strongly associated with insulin-resistance (IR), Studies have shown that IR plays a primary role in NAFLD pathogenesis. Recently it was reported that higher receptor activity of peroxisome proliferator-activated receptorγ(PPARγ) improved the body's sensitivity to insulin. Single nucleotide polymorphism (SNP) of PPARγis associated with metabolic syndrome (MS). As it is well known that NAFLD and MS share the same pathogeneses (IR), it is important to investigate the association between genetic and hereditary diseases with haplotype analysis. NAFLD is a kind of complicated gene disease, and the pathogeneses of NAFLD are still unclear. The aims of this study were to investigate the distributions of the PPARγhaplotypes of Cantonese Han patients with NAFLD and to explore the relationship between PPARγgene polymorphisms and NAFLD susceptibility.Methods:On the basis of our epidemiological survey in 2009, 232 moderate and severe fatty liver disease patients were selected. After removed 63 cases who were involved in drinking, viral hepatitis and drug-induced liver disease, this case-controlled study enrolled 169 Cantonese Han subjects with NAFLD as cases. According to the case for 1:3 proportion ratio, 699 subjects were randomly selected as controls among 1174 non-fatty liver disease persons. Polymerase chain reaction-restricted fragments length polymorphism (PCR-RFLP) was used to determine the single nucleotide polymorphisms (SNPs) in the four sites of PPARγgene (C-681G C-689T Pro12Ala and C1431T). Fasting plasma glucose (FPG), total cholesterol (CHOL) and triglyceride (TG) were tested by biochemistry. Anthropometrical parameters such as waist circumference, hip circumference, body height, body weight, blood pressure were measured. Age, drinking and living habits were collected in a standard questionnaire. Hardy-Weinberg law was used to confirm the sampling representatives. Linkage disequilibrium law was used to detect linkage strength. Logistic regression analysis was used to investigate the association between PPARγSNPs and NAFLD susceptibility. Haplotypes analysis was used to investigate the association of haplotypes with NAFLD susceptibility.Results:1. As compared with controls, body weight, BMI, waist circumference, hip circumference, WHR, SBP, DBP, FPG, fasting insulin, HOMA-IR, TG, CHOL, AST and ALT levels of NAFLD group were significantly increased, and HLDL level of which was significantly decreased.(P<0.05).2. The prevalence of MS in NAFLD group (60.94%) was significantly higher than that in controls (7.43%) (P<0.01).3. The CC,CG,GG genotype frequencies of C-681G polymorphisms in NAFLD group that were 0.349,0.479 and 0.172 differed significantly from those in controls that were 0.415,0.473 and 0.112. The SNPs in other three sites (C-689T, Pro12Ala, C1431T) were not significantly different from those of controls (P=0.03).4. The GG genotype of C-681G was an independent risk factor for NAFLD susceptibility (OR=2.04,95%CI:1.11-3.77,P=0.02).5. In haplotype analysis, GCCT haplotype was a risk factor for NAFLD susceptibility (OR=1.38, 95%CI:1.04-1.83,P=0.03).Conclusion:1. The clinical manifestations NAFLD and MS overlapped.2. PPARγgene C-681G polymorphism was closly associated with NAFLD 3. PPARγgene C-689T, Pro12Ala and C1431T polymorphisms were not associated with NAFLD susceptibility.4. PPARγgene GCCT haplotype was associated with NAFLD susceptibility.