The -308 TNFalpha gene polymorphism in severe acute alcoholic hepatitis: identification of a new susceptibility marker.
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.
Nguyen-Khac
Eric
E
Hepatogastroenterology Service, Amiens University Medical Center, Amiens Cedex, France. nguyen-khac.eric@chu-amiens.fr
Houchi
Hakim
H
Daoust
Martine
M
Dupas
Jean Louis
JL
Naassila
Mickaël
M
D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006519:Hepatitis, Alcoholic / Q000097:blood / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D006801:Humans; D008103:Liver Cirrhosis / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000235:genetics*
D000305:Adrenal Cortex Hormones; D014409:Tumor Necrosis Factor-alpha