Yonago Acta medica 2007;50:89–97
Association of Functional Gene Polymorphisms of Interleukin-1β and Transforming Growth Factor-β1 with the Progression of Liver Fibrosis in Japanese Patients with Hepatitis C Virus-Related Chronic Liver Disease
Mari Mandai, Yoshikazu Murawaki, Kinya Okamoto, Hideyuki Ohtani, Naoto Maeda and Isao Yuasa*
Division of Medicine and Clinical Science, Department of Multidisciplinary Internal Medicine, School of Medicine, Tottori University Faculty of Medicine, Yonago 683-8504 and *Division of Legal Medicine, Department of Social Medicine, School of Medicine, Tottori University Faculty of Medicine, Yonago 683-8503 Japan
Interleukin-1β (IL-1β) and interleukin-1 receptor antagonist (IL-1RN) are key cytokines in an inflammatory response, and transforming growth factor β1 (TGF-β1) promotes hepatic fibrogenesis. The association of polymorphisms in the genes for these cytokines with liver fibrosis is controversial. The aim of this study was to examine the possible association of IL-1β, IL-1RN and TGF-β1 polymorphisms with the progression of liver fibrosis in the Japanese population using cross-sectional and longitudinal study designs. We examined 183 patients with hepatitis C virus (HCV)-related chronic liver disease (93 chronic hepatitis and 90 with cirrhosis). Some of the chronic hepatitis cases were divided into progressive fibrosis and non-progressive fibrosis. IL-1β –31T/C, IL-1RN variable number of tandem repeats (VNTR) and TGF-β1 +869 T/C polymorphisms were analyzed using a polymerase-chain reaction-based assay. In the cross-sectional study, there were no significant differences in the genotype distributions of IL-1β, IL-1RN and TGF-β1 between chronic hepatitis and liver cirrhosis. No significant differences were found among Child-Pugh grades in cirrhosis patients. In the longitudinal study, there were no significant differences in the genotype distributions of IL-1β, IL-1RN and TGF-β1 between progressive fibrosis and non-progressive fibrosis. No significant differences in the speed at which liver fibrosis develop were found among the genotypes of IL-1β, IL-1RN and TGF-β1. In disagreement with other studies, the functional gene polymorphisms of IL-1β, IL-1RN and TGF-β1 were not associated with the progression of liver fibrosis in Japanese patients with HCV-related chronic liver disease.
Key words: interleukin-1β; interleukin-1 receptor antagonist; liver fibrosis; polymorphism; transforming growth factor-β1
