Interleukin-1beta gene polymorphisms associated with hepatocellular carcinoma in hepatitis C virus infection.
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-1beta and IL-1ra) and tumor necrosis factor-alpha (TNF-alpha), 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-1beta-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-1beta-31 and -511 loci were in near complete linkage disequilibrium, and the IL-1beta-511/-31 haplotype C-T was significantly associated with the presence of HCC (odds ratio of 1.51, P =.02). Polymorphisms in the TNF-alpha gene were not associated with disease. A multivariate analysis revealed that the IL-1beta-31 T/T genotype, alpha-fetoprotein >20 microg/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-1beta-31 genotype T/T or the IL-1beta-511/-31 haplotype C-T is associated with the presence of HCC in Japanese patients with chronic HCV infection.
Wang
Yue
Y
Department of Gastroenterology, Graduate School of Medicine, University of Tokyo, Japan.
Kato
Naoya
N
Hoshida
Yujin
Y
Yoshida
Hideo
H
Taniguchi
Hiroyoshi
H
Goto
Tadashi
T
Moriyama
Masaru
M
Otsuka
Motoyuki
M
Shiina
Shuichiro
S
Shiratori
Yasushi
Y
Ito
Yoichi
Y
Omata
Masao
M
D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000453:epidemiology / Q000235:genetics* / Q000821:virology; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D005838:Genotype; D019698:Hepatitis C, Chronic / Q000453:epidemiology / Q000235:genetics*; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics*; D008113:Liver Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000821:virology; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012307:Risk Factors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha