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The −308 TNFα Gene Polymorphism in Severe Acute Alcoholic Hepatitis: Identification of a New Susceptibility Marker
Author(s) -
NguyenKhac Eric,
Houchi Hakim,
Daoust Martine,
Dupas Jean Louis,
Naassila Mickaël
Publication year - 2008
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/j.1530-0277.2008.00629.x
Subject(s) - genotype , cirrhosis , medicine , alcoholic hepatitis , gastroenterology , tumor necrosis factor alpha , allele , allele frequency , alcoholic liver disease , biology , gene , genetics
Background: This study investigated whether genetic polymorphisms in the tumor necrosis factor alpha (TNFα) 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 TNFα polymorphisms (−238, −308, −863) using a polymerase chain reaction‐restriction fragment length polymorphism technique. Serum TNFα levels were determined. Results The TNFα−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 TNFα−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 TNFα 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 TNFα−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 TNFα 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 TNFα‐related genetic factors in susceptibility to AAH.