Are genetic polymorphisms of tumour necrosis factor alpha, interleukin-10, CD14 endotoxin receptor or manganese superoxide dismutase associated with alcoholic liver disease?
BACKGROUND
Four polymorphisms have been described associated with either increased risk for alcoholic liver disease (ALD) or more serious histological lesions: tumour necrosis factor alpha (TNF-alpha) G(-238)A, interleukin-10 (IL-10) C(-627)A, promoter of CD14 endotoxin receptor gene C(-159)T and manganese superoxide dismutase (MnSOD) C(-1183)T/valine --> alanine.


METHODS
We sought confirmatory evidence, through individual and simultaneous analysis of the four aforementioned polymorphisms, in 176 heavy drinkers: ALD (n = 100) if histology-compatible or clinical evidence of hepatic decompensation; and no evidence of liver disease (NLD) (n = 76) if normal liver tests on two occasions or normal liver histology (steatosis alone).


RESULTS
Patients with ALD were older (53+/-10 vs. 48+/-10 years, P<0.05), with a similar sex distribution. TNF-alpha G(-238)A showed no difference in heterozygous GA-genotype prevalence (ALD, 9.0%/NLD, 7.9%). IL-10 C(-627)A showed no difference between groups, either homozygote AA (8.0% vs. 10.5%) or heterozygote CA (34.0% vs. 39.5%). CD14 promoter C(-159)T showed no difference between groups in T-allele frequency, either homozygote TT (27% vs. 21%) or heterozygote CT (49% vs. 50%). Alanine MnSOD allele carriers showed no difference between groups in either the heterozygote (55.0% vs. 49.3%) or homozygote (22% vs. 25%). No difference was observed in the probability of having simultaneously two, three or four of the implicated polymorphisms: respectively, 43%, 33% and 0% in ALD, and 43%, 24% and 5% in NLD (not significant).


CONCLUSIONS
No association was found between the previously implicated polymorphisms of TNF-alpha, IL-10, CD14 and MnSOD, either individually or simultaneously, and the presence of established ALD.
Martins
Alexandra
A
Unidade de Nutrição e Metabolismo, Lisbon, Portugal.
Cortez-Pinto
Helena
H
Machado
Mariana
M
Gonçalves
Maria Sara
MS
Soren
Steffensen
S
Marques-Vidal
Pedro
P
de Moura
Miguel Carneiro
MC
Camilo
Maria Ermelinda
ME
D000328:Adult; D000428:Alcohol Drinking / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics; D018950:Lipopolysaccharide Receptors / Q000235:genetics; D008108:Liver Diseases, Alcoholic / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D013482:Superoxide Dismutase / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D018950:Lipopolysaccharide Receptors; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D013482:Superoxide Dismutase