Association between rs738408, rs738409 and rs139051polymorphisms in PNPLA3 gene and non-alcoholic fatty liver disease

To date, Patatin-like phospholipase domain-containing protein 3 (PNPLA3) polymorphisms have been considered to be a modifier of the non-alcoholic fatty liver disease (NAFLD) in some people from different racial/ethnic groups worldwide. The aim of the current study was the investigation of the possible association between PNPLA3 gene genetic variants and susceptibility to NAFLD in Iranian population. After peripheral blood samples have been taken from 100 patients diagnosed with NAFLD and 200 control individual, subject DNAs were analyzed for possible genetic variants by both PCR-SSCP and targeted sequencing techniques. The logistic regression model was applied to examine the distribution of PNPLA3 gene polymorphisms between the studied groups and the clinic pathological characteristics of NAFLD in SAS 9.1 software. In this study, one intronic (rs139051) and two exonic (rs738408, and rs738409) single nucleotide polymorphisms (SNP) were observed in PNPLA3. Both rs738409 and rs738408 are in tight linkage disequilibrium. Based on our results, the rs738409 GG or GC, and rs738408 TT or TC genotypes were associated with increased risk of NAFLD( P = 0.004). Moreover, the AG + GG combined genotype of rs139051was found to be associated with a decreased risk for NAFLD by 0.58-fold ((95%CI: 0.342–0.984), P = 0.04).Additionally, our analysis revealed a remarkable association between rs139051 SNP and the levels of fasting blood sugar in patients( P = 0.0438). Our study confirmed that both rs738409 and rs738408 are associated with NAFLD. Also, PNPLA3 rs139051 polymorphism may be a genetic risk factor for susceptibility to having higher levels of FBS. • rs738409 is associated with NAFLD. • rs738408 is associated with NAFLD. • PNPLA3 rs139051 polymorphism may be a genetic risk factor for susceptibility to having higher levels of FBS.