Interaction of <i>SAMM50-rs738491</i> , <i>PARVB-rs5764455</i> and <i>PNPLA3-rs738409</i> Increases Susceptibility to Nonalcoholic Steatohepatitis
Ke Xu, Kenneth I. Zheng, Pei‐Wu Zhu, Wen‐Yue Liu, Hong‐Lei Ma, Gang Li, Liang‐Jie Tang, Rafael S. Rios, Giovanni Targher, Christopher D. Byrne, Xiaodong Wang, Yong‐Ping Chen, Ming‐Hua Zheng
Abstract
Background and Aims: are associated with nonalcoholic fatty liver disease (NAFLD). However, no studies have examined the effect of interactions between these three genotypes to affect liver disease severity. We assessed the effect of these three SNPs on nonalcoholic steatohepatitis (NASH) and also examined the gene-gene interactions in a Chinese population with biopsy-confirmed NAFLD. Methods: . Gene-gene interactions were analyzed by performing a generalized multifactor dimensionality reduction (GMDR) analysis. Results: GG genotypes had a higher risk of NASH, even after adjustment for age, sex and body mass index. GMDR analysis showed that the combination of all three SNPs was the best model for predicting NASH. Additionally, the odds ratio of the haplotype T-A-G for predicting the risk of NASH was nearly three times higher than that of the haplotype G-C-C. Conclusions: GG genotypes are at greater risk of NASH. These three SNPs may synergistically interact to increase susceptibility to NASH.