Tumor necrosis factor gene polymorphisms in patients with cirrhosis from chronic hepatitis C virus infection

Academic Article

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.
  • Published In

  • Genes and Immunity  Journal
  • Digital Object Identifier (doi)

    Author List

  • Yee LJ; Tang J; Herrera J; Kaslow RA; Van Leeuwen DJ
  • Start Page

  • 386
  • End Page

  • 390
  • Volume

  • 1
  • Issue

  • 6