BACKGROUND & AIMS:
The PNPLA3 rs738409 C>G polymorphism (encoding for I148M) has recently been identified as a susceptibility factor for steatosis-mediated liver damage. We evaluated the influence of this polymorphism on hepatocarcinogenesis in patients with chronic hepatitis C (CHC) virus infection.
We genotyped the rs738409 single-nucleotide polymorphism in 358 hepatitis C-associated hepatocellular carcinoma (HCC) patients and correlated the age at onset of HCC and the interval between hepatitis C virus (HCV) infection and the development of HCC in patients with each genotype.
The frequencies of CC, CG, and GG genotypes were 27.9% (100/358), 49.2% (176/358), and 22.9% (82/358), respectively, and were in Hardy-Weinberg equilibrium. The median age at onset of HCC for the GG genotype was significantly younger compared to for non-GG genotypes (67.81 vs. 69.87 years, P < 0.001), and the median interval between HCV infection and the development of HCC was significantly shorter in patients with the GG genotype (39.96 vs. 40.85 years, P = 0.008). PNPLA3 GG genotype was also associated with a higher AST level (69.5 vs. 59.0 IU/l, P = 0.02), lower prothrombin time (73.0% vs. 78.0%, P = 0.008), and a higher prevalence of histological steatosis (40.0% vs. 22.2%, P = 0.01) at the time of HCC onset.
The PNPLA3 genotype GG may be associated with accelerated hepatocarcinogenesis in CHC patients through increased steatosis in the liver.