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Interleukin‐1β gene polymorphisms associated with hepatocellular carcinoma in hepatitis C virus infection
Author(s) -
Wang Yue,
Kato Naoya,
Hoshida Yujin,
Yoshida Hideo,
Taniguchi Hiroyoshi,
Goto Tadashi,
Moriyama Masaru,
Otsuka Motoyuki,
Shiina Shuichiro,
Shiratori Yasushi,
Ito Yoichi,
Omata Masao
Publication year - 2003
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1053/jhep.2003.50017
Subject(s) - odds ratio , hepatocellular carcinoma , hepatitis c virus , genotype , interleukin 28b , medicine , gastroenterology , linkage disequilibrium , cirrhosis , haplotype , immunology , liver disease , hepatitis c , genotyping , biology , virus , genetics , gene , ribavirin
Hepatitis C virus (HCV) infection is a major risk factor for developing hepatocellular carcinoma (HCC), a life‐threatening sequel. However, the factors that affect disease progression to HCC have not been thoroughly elucidated. Genetic polymorphisms in proinflammatory cytokines, the interleukin 1 (IL‐1) family (IL‐1β and IL‐1ra) and tumor necrosis factor‐α (TNF‐α), were studied in 274 Japanese patients with chronic HCV infection and 55 healthy individuals using standard polymerase chain reaction‐based genotyping techniques. The association between these polymorphisms and disease status was evaluated while controlling for confounding clinical variables. The proportion of patients with HCC in the IL‐1β‐31 T/T (55%, odds ratio to C/C was 2.63, P = .009) genotype was higher than in the T/C (44%, odds ratio to C/C was 1.64, P = .149) and C/C genotypes (35%). The IL‐1β‐31 and ‐511 loci were in near complete linkage disequilibrium, and the IL‐1β‐511/‐31 haplotype C‐T was significantly associated with the presence of HCC (odds ratio of 1.51, P = .02). Polymorphisms in the TNF‐α gene were not associated with disease. A multivariate analysis revealed that the IL‐1β‐31 T/T genotype, α‐fetoprotein >20 μg/L, presence of cirrhosis, male sex, and age >60 years were associated with the presence of HCC at odds ratios of 3.73 (T/T vs. C/C), 4.12, 4.03, 3.89, and 3.27, respectively. In conclusion, the IL‐1β‐31 genotype T/T or the IL‐1β‐511/‐31 haplotype C‐T is associated with the presence of HCC in Japanese patients with chronic HCV infection.