Interaction of , and Increases Susceptibility to Nonalcoholic Steatohepatitis.

BACKGROUND AND AIMS

Previous studies have reported that the single nucleotide polymorphisms (SNPs) of and 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

We enrolled 415 consecutive adult individuals with biopsy-proven NAFLD. Multivariable logistic regression analysis was undertaken to test associations between NASH and SNPs in and . Gene-gene interactions were analyzed by performing a generalized multifactor dimensionality reduction (GMDR) analysis.

RESULTS

The mean ± standard deviation age of these 415 patients was 41.3±12.5 years, and 75.9% were men. Patients with TT, AA or 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

NAFLD patients carrying the TT, AA or GG genotypes are at greater risk of NASH. These three SNPs may synergistically interact to increase susceptibility to NASH.