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Impact of PNPLA3 polymorphisms on the development of hepatocellular carcinoma in patients with chronic hepatitis C virus infection
Author(s) -
Sato Masaya,
Kato Naoya,
Tateishi Ryosuke,
Muroyama Ryosuke,
Kowatari Norie,
Li Wenwen,
Goto Kaku,
Otsuka Motoyuki,
Shiina Shuichiro,
Yoshida Haruhiko,
Omata Masao,
Koike Kazuhiko
Publication year - 2014
Publication title -
hepatology research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.123
H-Index - 75
eISSN - 1872-034X
pISSN - 1386-6346
DOI - 10.1111/hepr.12258
Subject(s) - hepatocellular carcinoma , genotype , steatosis , gastroenterology , medicine , hepatitis c virus , single nucleotide polymorphism , hepatitis b virus , chronic hepatitis , hepatitis c , virus , immunology , biology , gene , genetics
Aim 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 H ardy– W einberg 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. Conclusion The PNPLA3 genotype GG may be associated with accelerated hepatocarcinogenesis in CHC patients through increased steatosis in the liver.