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

Research output: Contribution to journalArticle

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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

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Virus Diseases
Interleukin-1
Hepacivirus
Hepatocellular Carcinoma
Genes
Odds Ratio
Genotype
Chronic Hepatitis C
Haplotypes
Genotyping Techniques
Tumor Necrosis Factor-alpha
Fetal Proteins
Confounding Factors (Epidemiology)
Linkage Disequilibrium
Genetic Polymorphisms
Disease Progression
Fibrosis
Multivariate Analysis
Cytokines
Polymerase Chain Reaction

ASJC Scopus subject areas

  • Hepatology

Cite this

Interleukin-1β gene polymorphisms associated with hepatocellular carcinoma in hepatitis C virus infection. / Wang, Yue; Kato, Naoya; Hoshida, Yujin; Yoshida, Hideo; Taniguchi, Hiroyoshi; Goto, Tadashi; Moriyama, Masaru; Otsuka, Motoyuki; Shiina, Shuichiro; Shiratori, Yasushi; Ito, Yoichi; Omata, Masao.

In: Hepatology, Vol. 37, No. 1, 01.01.2003, p. 65-71.

Research output: Contribution to journalArticle

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, vol. 37, no. 1, pp. 65-71. https://doi.org/10.1053/jhep.2003.50017
Wang, Yue ; Kato, Naoya ; Hoshida, Yujin ; Yoshida, Hideo ; Taniguchi, Hiroyoshi ; Goto, Tadashi ; Moriyama, Masaru ; Otsuka, Motoyuki ; Shiina, Shuichiro ; Shiratori, Yasushi ; Ito, Yoichi ; Omata, Masao. / Interleukin-1β gene polymorphisms associated with hepatocellular carcinoma in hepatitis C virus infection. In: Hepatology. 2003 ; Vol. 37, No. 1. pp. 65-71.
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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.",
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AU - Kato, Naoya

AU - Hoshida, Yujin

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AU - Taniguchi, Hiroyoshi

AU - Goto, Tadashi

AU - Moriyama, Masaru

AU - Otsuka, Motoyuki

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AU - Shiratori, Yasushi

AU - Ito, Yoichi

AU - Omata, Masao

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AB - 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.

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