Abstract
Pro-inflammatory cytokines including tumour necrosis factor (TNF) mediate the pathogenesis of hepatitis C virus (HCV) infection. The distribution of TNF gene polymorphisms was examined among cirrhotic and non-cirrhotic patients infected with HCV. Thirty Caucasians with cirrhosis due to chronic HCV infection and 114 HCV-infected patients histopathologically free of cirrhosis were genotyped for genetic variants in TNF, lymphotoxin α and TNF-receptor type I using PCR-based techniques. Variability in the progression of HCV-related cirrhosis was assessed in a multivariate model including genetic and non-genetic factors such as gender, estimated duration of infection, alcohol consumption, and viral genotype. Viral genotype and non-genetic host features were not independently related to the occurrence or rate of development of cirrhosis in the patient population. In contrast, the TNF promoter variants TNF2 (−238A) and TNF3 (−308A) conferred a 3.2-fold and 5.1-fold risk of cirrhosis respectively (P = 0.03 for both). Reciprocal effects were observed with several TNF alleles and haplotypes defined by the −238G/A and −308G/A dimorphic sequences. Polymorphisms in the TNFα promoter appear to be associated with variability in the histological severity of chronic hepatitis C infection.
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Grant Support: LJY was supported by a special grant from the Alabama Chapter of the American Liver Foundation to the UAB Liver Center and a gift from Mrs. Marie Ingalls to the UAB Liver Center. A portion of this study was made possible by an unrestricted grant in aid of hepatitis C research from Schering-Plough/Integrated Therapeutics Inc. to the UAB Liver Center (DJvL).
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Yee, L., Tang, J., Herrera, J. et al. Tumor necrosis factor gene polymorphisms in patients with cirrhosis from chronic hepatitis C virus infection. Genes Immun 1, 386–390 (2000). https://doi.org/10.1038/sj.gene.6363696
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DOI: https://doi.org/10.1038/sj.gene.6363696