Influence of TNF gene polymorphism in patients with acute and fulminant hepatitis.

Abstract

BACKGROUND:

Tumor necrosis factor (TNF) is involved in liver damage, especially in fulminant hepatitis (FH). Our previous data showed that the serum level of TNF-alpha was markedly increased in FH. To investigate the mechanism of the overproduction of TNF in FH patients, polymorphism of the TNF gene was studied.

METHODS:

We analyzed 120 healthy subjects (controls), 63 patients with acute hepatitis (AH), and 32 patients with FH. Of the 32 FH patients, 21 died or received liver transplantation (FH-D), and 11 survived with intensive therapy (FH-S). The TNF-alpha promoter region at -1031, -863, -857, -308, and -238, and TNF-beta Nco1 polymorphism sites were studied.

RESULTS:

(1) The four groups showed no differences in polymorphisms of positions -857, -308, and -238. The allelic frequencies of positions -1031C and -863A in the FH-D patients were significantly higher compared to findings in control subjects. (2) The allelic frequency of B2 in the TNF-beta gene was significantly higher in FH patients, and particularly in the FH-D patients, compared to control subjects. (3) When the patients were divided into four groups by etiology, hepatitis A virus (HAV), HBV, HCV, and non-A non-B non-C, the allelic frequencies of positions -863A and TNF-beta B2 in FH patients were increased in the non-A non-B non-C group compared to controls.

CONCLUSIONS:

FH patients with a poor prognosis had higher frequencies of positions -1031C and -863A in the TNF-alpha promoter region, and higher frequencies of the B2 allele of the TNF-beta gene. These data suggest that the genomic background may be associated with the prognosis of acute liver failure.

• Authors: Noriko Tsuchiya, Katsutoshi Tokushige, Naoko Yamaguchi, Kiyoshi Hasegawa, Etsuko Hashimoto, Katsumi Yamauchi, Keiko Shiratori
• Journal: Journal of gastroenterology (J Gastroenterol) Vol. 39 Issue 9 Pg. 859-66 (Sep 2004) ISSN: 0944-1174 [Print] Japan
• PMID: 15565405 (Publication Type: Journal Article)

Chemical References

• Tumor Necrosis Factor-alpha

Topics

• Acute Disease
• Adult
• Asian People (genetics)
• Female
• Gene Frequency
• Humans
• Liver Failure, Acute (genetics, mortality)
• Male
• Middle Aged
• Polymorphism, Genetic
• Prognosis
• Promoter Regions, Genetic
• Tumor Necrosis Factor-alpha (genetics)