Viral genotype-specific role of PNPLA3 , PPARG , MTTP, and IL28B in hepatitis C virus-associated steatosis

Background & Aims Steatosis is a prominent feature of hepatitis C, especially in patients infected with genotype 3. The analysis of genetic polymorphisms influencing steatosis in chronic hepatitis C has been limited by the studies’ small sample size, and important single nucleotide polymorphisms (SNPs), such as those in the patatin-like phospholipase family 3 protein ( PNPLA3 ), were never evaluated. Methods We analyzed the role of SNPs, from 19 systematically selected candidate genes, on steatosis in 626 Caucasian hepatitis C virus (HCV) infected patients. SNPs were extracted from a genome-wide association-generated dataset. Associations of alleles with the presence and/or different severity of steatosis were evaluated by univariate and multivariate logistic regression, accounting for all relevant covariates. Results The risk of steatosis was increased by carriage of I148 M in PNPLA3 , but only in patients with HCV genotypes non-3 (odds ratio [OR] = 1.9, 95% confidence interval [CI] = 1.6–2.3, p