title: Are genetic polymorphisms of tumour necrosis factor alpha, interleukin-10, CD14 endotoxin receptor or manganese superoxide dismutase associated with alcoholic liver disease?
abstract: 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.
authors.affiliation: Unidade de Nutrição e Metabolismo, Lisbon, Portugal.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Martins
authors.forename: Helena
authors.initials: H
authors.lastname: Cortez-Pinto
authors.forename: Mariana
authors.initials: M
authors.lastname: Machado
authors.forename: Maria Sara
authors.initials: MS
authors.lastname: Gonçalves
authors.forename: Steffensen
authors.initials: S
authors.lastname: Soren
authors.forename: Pedro
authors.initials: P
authors.lastname: Marques-Vidal
authors.forename: Miguel Carneiro
authors.initials: MC
authors.lastname: de Moura
authors.forename: Maria Ermelinda
authors.initials: ME
authors.lastname: Camilo
mesh_terms: 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
chemical_list: D018950:Lipopolysaccharide Receptors; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D013482:Superoxide Dismutase