Does the simultaneous tumor necrosis factor receptor 2, tumor necrosis factor promoter gene polymorphism represent a higher risk for alcoholic liver disease?
OBJECTIVE
Tumor necrosis factor alpha (TNF-alpha) is a proinflammatory cytokine that seems to play a crucial role in the pathogenesis of alcoholic liver disease (ALD). TNF-alpha exerts its effects by binding to specific receptors (TNFR); the polymorphism of TNFRII T587G has been associated with increased TNF apoptotic response and its presence may increase the risk to develop liver disease. The aim of this study was to evaluate the prevalence of the TNF-alpha G238A promoter and TNFRII polymorphisms, individually or simultaneously, in ALD.


METHODS
TNF-alpha G238A and TNFRII T587G polymorphisms were studied in 103 unrelated patients with ALD (biopsy confirmed or clinical evidence) and in 76 heavy drinkers without liver disease (NLD). Single nucleotide polymorphism gene was detected by a polymerase chain reaction-restriction fragment length polymorphisms method. All patients had, at least, a 5 year history of alcohol consumption greater than 80 g/day.


RESULTS
TNF-alpha G238A allele frequency was similar in both groups. TNFRII T587G allele frequency was slightly higher in the ALD group than in the NLD group (21 vs. 18%, P=NS). TNF-alpha G238A and TNFRII T587G were simultaneously present in six ALD patients and in none of NLD patients (P=0.04).


CONCLUSIONS
Although individually there was no association between TNFRII T587G or TNF-alpha G238A polymorphisms and ALD, this study suggests that the presence of both polymorphisms may enhance the susceptibility for ALD. TNF-alpha G238A may increase TNF-alpha production, which when associated with TNFRII T587G, can further exacerbate TNF-alpha response leading to a greater risk of ALD.
Machado
Mariana Verdelho
MV
Department of Gastroenterology Hospital Santa Maria, Lisbon, Portugal.
Martins
Alexandra
A
Almeida
Rosário
R
Marques-Vidal
Pedro
P
Gonçalves
Maria S
MS
Camilo
Maria E
ME
Cortez-Pinto
Helena
H
D000328:Adult; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D008108:Liver Diseases, Alcoholic / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha