Association of a tumor necrosis factor promoter polymorphism with susceptibility to alcoholic steatohepatitis

Hepatology. 1997 Jul;26(1):143-6. doi: 10.1002/hep.510260119.


Twin concordance studies suggest that genetic factors play a role in determining why only a minority of heavy drinkers develop hepatitis and cirrhosis. Tumor necrosis factor alpha (TNF-alpha) has emerged as the "final common pathway" in the pathogenesis of alcohol-related hepatic necro-inflammation. We have examined the frequency of the two recently described polymorphisms of the TNF-alpha promoter in 150 patients with biopsy-proven alcoholic liver disease and 145 healthy volunteers. There was a significant excess of the rare allele (TNFA-A; G(-238) --> A) at position -238 in patients with steatohepatitis compared with controls or patients without this lesion. This is consistent with previous suggestions that the TNFA-A allele, which falls within a putative Y regulation box of the TNF-alpha promoter, is associated with increased TNF-alpha expression. No differences were observed for the polymorphism at position -308.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Hepatitis, Alcoholic / genetics*
  • Humans
  • Liver Cirrhosis, Alcoholic / genetics*
  • Polymorphism, Genetic*
  • Promoter Regions, Genetic / genetics*
  • Sex Factors
  • Tumor Necrosis Factor-alpha / genetics*


  • Tumor Necrosis Factor-alpha