Interleukin-1β gene polymorphisms associated with hepatocellular carcinoma in hepatitis C virus infection

Yue Wang, Naoya Kato, Yujin Hoshida, Hideo Yoshida, Hiroyoshi Taniguchi, Tadashi Goto, Masaru Moriyama, Motoyuki Otsuka, Shuichiro Shiina, Yasushi Shiratori, Yoichi Ito, Masao Omata

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151 Scopus citations

Abstract

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-1 ra) 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.

Original languageEnglish (US)
Pages (from-to)65-71
Number of pages7
JournalHepatology
Volume37
Issue number1
DOIs
StatePublished - Jan 1 2003
Externally publishedYes

ASJC Scopus subject areas

  • Hepatology

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    Wang, Y., Kato, N., Hoshida, Y., Yoshida, H., Taniguchi, H., Goto, T., Moriyama, M., Otsuka, M., Shiina, S., Shiratori, Y., Ito, Y., & Omata, M. (2003). Interleukin-1β gene polymorphisms associated with hepatocellular carcinoma in hepatitis C virus infection. Hepatology, 37(1), 65-71. https://doi.org/10.1053/jhep.2003.50017