Interaction Between AGTR1 and PPARγ Gene Polymorphisms on the Risk of Nonalcoholic Fatty Liver Disease.

Aims: Nonalcoholic fatty liver disease (NAFLD) is an important public health issue worldwide. Several recent studies have reported that peroxisome proliferator-activated receptor-gamma (PPAR gamma) and angiotensin II type 1 receptor (AGTR1) variants are associated with NAFLD occurrence, but the results have been inconsistent. The aim of this study was to analyze the interactions between PPAR gamma and AGTR1 polymorphisms and their associations with NAFLD in Chinese adults. Methods: Seven single nucleotide polymorphisms (SNPs) of the PPAR gamma gene and 5 SNPs of the AGTR1 gene were selected and genotyped in 1591 unrelated Chinese adults. The SNPAssoc package of R was used to examine the relationships between the selected SNPs and NAFLD. Results: After adjusting the covariance, the results from the overdominant model showed that participants carrying the T/C genotype of rs2638360 in AGTR1 have a decreased risk of NAFLD compared with those with T/T-C/C genotypes (odds ratio: 0.70, 95% confidence interval: 0.49-1.00). However, our results showed that none of the selected PPAR gamma variants were significantly associated with the risk of NAFLD after applying a false discovery rate correction. Among the 12 selected SNPs from PPAR gamma and AGTR1, model-based multifactor dimensionality reduction (MB-MDR) analyses for gene-gene interactions revealed that all the models were significantly associated with the increased risk of NAFLD (p < 0.05) except the 2-, 10-, 11-, and 12-locus models. Further, among the 10 SNPs negatively associated with NAFLD, the four-locus model (rs13431696 and rs3856806 in PPAR gamma, and rs5182, rs1492100 in ATGR1) and the five-locus model (rs9817428, rs1175543, rs13433696, and rs2920502 in PPAR gamma, and rs1492100 in ATGR1) were closely related with NAFLD susceptibility (p = 0.019 and p = 0.048, respectively). Conclusion: Our present study suggests that interactions among multiple AGTR1 and PPAR gamma polymorphisms are associated with the risk of NAFLD in the Chinese population.