The interaction of SAMM50-rs738491, PARVB-rs5764455 and PNPLA3-rs738409 increases the susceptibility to nonalcoholic steatohepatitis

Background: Previous studies have reported that single nucleotide polymorphisms (SNPs) in SAMM50-rs738491, PARVB-rs5764455 and PNPLA3-rs738409 are associated with the development of non-alcoholic fatty liver disease (NAFLD). However, no studies have examined the effect of interactions between these three genotypes to affect liver disease severity. Objective: Our aim was to assess the effect of these three SNPs on nonalcoholic steatohepatitis (NASH) and to investigate gene-gene interactions in a Chinese cohort of patients with biopsy-proven NAFLD. Methods: : 415 adult patients with biopsy-proven NAFLD were recruited to the study. Multivariable logistic regression analysis was undertaken to test associations between NASH and SNPs in SAMM50-rs738491, PARVB-rs5764455 and PNPLA3-rs738409 . Gene-gene interactions were analyzed by performing a generalized multifactor dimensionality reduction (GMDR) analysis. Results: : The mean age of patients was 41.3±12.5 years and 75.9% of them were men. Patients with SAMM50-rs738491 TT, PARVB-rs5764455 AA or PNPLA3-rs738409 GG genotypes had a higher risk of having NASH even after adjustment for age, sex and body mass index. Furthermore, GMDR analysis showed that the combination of all three SNPs was the best model to predict NASH. Additionally, the odds ratio of the haplotype A-G-T for predicting risk of NASH was nearly three times higher than that of the haplotype G-C-C. Conclusions: : Patients with NAFLD who have SAMM50-rs738491 TT, PARVB-rs5764455 AA or PNPLA3-rs738409 GG genotypes are at higher risk of NASH. Moreover, these SNPs synergistically interact to increase the susceptibility to NASH.