Lack of association between tumour necrosis factor receptor types 1 and 2 gene polymorphism and severe acute alcoholic hepatitis.
OBJECTIVE
Tumour necrosis factor-alpha (TNF-alpha) is involved in the physiopathology of severe acute alcoholic hepatitis (AAH) binding with TNF receptor types TNFR1 and TNFR2, whose serum concentrations are elevated. We studied the role of TNFR1 and TNFR2 gene polymorphism in AAH patients.


METHODS
One hundred and ninety-two patients (58 AAH with Maddrey score >or=32, 44 non-AAH cirrhoses, 90 healthy individuals) were genotyped for A36G TNFR1 and T676G TNFR2 using polymerase chain reaction-restriction fragment length polymorphism technique. Serum sTNFR1 and sTNFR2 were assayed.


RESULTS
The AAH and two control groups did not differ for genotype distribution. In three groups, A (36 TNFR1) and T (676 TNFR2) allelic frequencies were similar, at 0.47, 0.47, 0.44 and 0.78, 0.81, 0.80, respectively. The 36 TNFR1, 676 TFNR2 genotypes did not influence on prognostic scores (Maddrey, Child-Pugh), nor in response to corticosteroids or 6-month survival. sTNFR1 levels were higher in AAH than healthy group (3.07+/-1.14 vs. 1.17+/-0.27 ng/ml, P<0.001) and sTNFR2 levels were higher in AAH than cirrhosis (3.6+/-1.02 vs. 3.1+/-1.03, P<0.05) and healthy groups (3.6+/-1.02 vs. 1.91+/-0.54, P<0.001). However, sTNFR1 and sTNFR2 levels did not vary significantly according to genotypes.


CONCLUSIONS
These results did not support an association between 36 TNFR1, 676 TNFR2 gene polymorphisms and AAH.
Nguyen-Khac
Eric
E
Service d'Hépato-Gastroentérologie, Centre Hospitalier Universitaire d'Amiens, Amiens, 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; D056726:Genetic Association Studies; D006519:Hepatitis, Alcoholic / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000097:blood / Q000235:genetics*; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000097:blood / Q000235:genetics*
D000305:Adrenal Cortex Hormones; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II