title: Impact of PNPLA3 polymorphisms on the development of hepatocellular carcinoma in patients with chronic hepatitis C virus infection.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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 aspartate aminotransferase 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.
  
  
  CONCLUSIONS
  The PNPLA3 genotype GG may be associated with accelerated hepatocarcinogenesis in CHC patients through increased steatosis in the liver.
authors.affiliation: Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Masaya
authors.initials: M
authors.lastname: Sato
authors.forename: Naoya
authors.initials: N
authors.lastname: Kato
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Tateishi
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Muroyama
authors.forename: Norie
authors.initials: N
authors.lastname: Kowatari
authors.forename: Wenwen
authors.initials: W
authors.lastname: Li
authors.forename: Kaku
authors.initials: K
authors.lastname: Goto
authors.forename: Motoyuki
authors.initials: M
authors.lastname: Otsuka
authors.forename: Shuichiro
authors.initials: S
authors.lastname: Shiina
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Yoshida
authors.forename: Masao
authors.initials: M
authors.lastname: Omata
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Koike
keywords: fibrosis; hepatocarcinogenesis; risk allele; rs738409; steatosis