The -308 TNFalpha gene polymorphism in severe acute alcoholic hepatitis: identification of a new susceptibility marker.

Abstract

BACKGROUND:

This study investigated whether genetic polymorphisms in the tumor necrosis factor alpha (TNFalpha) gene's promoter region play a role in severe acute alcoholic hepatitis (AAH).

METHODS:

One-hundred and fifty patients (58 AAH patients, 45 cirrhosis group free-AAH, 47 healthy group) were genotyped for 3 TNFalpha polymorphisms (-238, -308, -863) using a polymerase chain reaction-restriction fragment length polymorphism technique. Serum TNFalpha levels were determined.

RESULTS:

The TNFalpha-308 allele A frequency was significantly lower in AAH group (0.09), than cirrhosis (0.28) (p < 0.001), and healthy groups (p < 0.001). The TNFalpha-308 A/G, A/A genotypes were significantly lower in AAH group, than cirrhosis (p = 0.005), and healthy groups (p < 0.001). For AAH group, there were no clinical, biological, and serum TNFalpha differences between the -308 G/G and A/G, A/A genotype patients, apart higher transaminase in the former group (p = 0.02). AAH and cirrhosis groups did not differ for the frequency of TNFalpha-238, -863 polymorphisms. The specific genotype did not appear to have any influence on the therapeutic response following corticotherapy or posttreatment 6-month survival. In the AAH group, nonsurvivors had higher TNFalpha levels than survivors (7.9 +/- 8.8 vs. 3.3 +/- 1.6 pg/ml, p = 0.01).

CONCLUSIONS:

These results attest to the involvement of TNFalpha-related genetic factors in susceptibility to AAH.

• Authors: Eric Nguyen-Khac, Hakim Houchi, Martine Daoust, Jean Louis Dupas, Mickaël Naassila
• Journal: Alcoholism, clinical and experimental research (Alcohol Clin Exp Res) Vol. 32 Issue 5 Pg. 822-8 (May 2008) ISSN: 1530-0277 [Electronic] England
• PMID: 18336639 (Publication Type: Journal Article)

Chemical References

• Adrenal Cortex Hormones
• Tumor Necrosis Factor-alpha

Topics

• Adrenal Cortex Hormones (therapeutic use)
• Adult
• Aged
• Female
• Genetic Predisposition to Disease
• Genotype
• Hepatitis, Alcoholic (blood, drug therapy, genetics, mortality)
• Humans
• Liver Cirrhosis (genetics)
• Male
• Middle Aged
• Polymorphism, Single Nucleotide
• Promoter Regions, Genetic
• Tumor Necrosis Factor-alpha (blood, genetics)