【摘 要】
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Background and Aims: Previous studies have reported that the single nucleotide polymorphisms (SNPs) of SAMM50-rs738491, PARVB-rs5764455 and PNPLA3-rs738409 are associated with nonalcoholic fatty liver disease (NAFLD). However, no studies have examined the
【机 构】
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NAFLD Research Center,Department of Hepatology,First Affiliated Hospital of Wenzhou Medical Universi
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Background and Aims: Previous studies have reported that the single nucleotide polymorphisms (SNPs) of SAMM50-rs738491, PARVB-rs5764455 and PNPLA3-rs738409 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 severi-ty. We assessed the effect of these three SNPs on nonalcohol-ic steatohepatitis (NASH) and also examined the gene-gene interactions in a Chinese population with biopsy-confirmed NAFLD. Methods: We enrolled 415 consecutive adult individ-uals with biopsy-proven NAFLD. Multivariable logistic regres-sion analysis was undertaken to test associations between NASH and SNPs in SAMM50-rs738491, PARVB-rs5764455 and PNPLA3-rs738409. Gene-gene interactions were ana-lyzed 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 SAMM50-rs738491 TT, PARVB-rs5764455 AA or PNPLA3-rs738409 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 predict-ing 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 pa-tients carrying the SAMM50-rs738491 TT, PARVB-rs5764455 AA or PNPLA3-rs738409 GG genotypes are at greater risk of NASH. These three SNPs may synergistically interact to increase susceptibility to NASH.
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