Association of a tumor necrosis factor promoter polymorphism with susceptibility to alcoholic steatohepatitis.
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.
Grove
J
J
Department of Medicine, University of Newcastle, Newcastle upon Tyne, UK.
Daly
A K
AK
Bassendine
M F
MF
Day
C P
CP
D000367:Age Factors; D006519:Hepatitis, Alcoholic / Q000235:genetics*; D006801:Humans; D008104:Liver Cirrhosis, Alcoholic / Q000235:genetics*; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012737:Sex Factors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D014409:Tumor Necrosis Factor-alpha