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

Genes Immun. 2000 Aug;1(6):386-90. doi: 10.1038/sj.gene.6363696.


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 alpha 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 TNF alpha promoter appear to be associated with variability in the histological severity of chronic hepatitis C infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Alleles
  • Antigens, CD / genetics
  • CD4 Antigens / genetics
  • Case-Control Studies
  • Female
  • Gene Frequency
  • Haplotypes
  • Hepatitis C, Chronic / complications
  • Hepatitis C, Chronic / genetics*
  • Hepatitis C, Chronic / immunology*
  • Humans
  • Liver Cirrhosis / etiology
  • Liver Cirrhosis / genetics*
  • Liver Cirrhosis / immunology*
  • Lymphotoxin-alpha / genetics
  • Male
  • Middle Aged
  • Polymorphism, Genetic
  • Receptors, Tumor Necrosis Factor / genetics
  • Receptors, Tumor Necrosis Factor, Type I
  • Tandem Repeat Sequences
  • Tumor Necrosis Factor-alpha / genetics*


  • Antigens, CD
  • CD4 Antigens
  • Lymphotoxin-alpha
  • Receptors, Tumor Necrosis Factor
  • Receptors, Tumor Necrosis Factor, Type I
  • Tumor Necrosis Factor-alpha