title: Interleukin 10 promoter region polymorphisms and susceptibility to advanced alcoholic liver disease.
abstract: BACKGROUND
  The factors determining why less than 10% of heavy drinkers develop advanced alcoholic liver disease (ALD) remain elusive, although genetic factors may be important. Interleukin 10 (IL-10) is an important cytokine with anti-inflammatory, anti-immune, and antifibrotic functions. Several polymorphisms have been identified in the IL-10 promoter and recent evidence suggests that some of these may have functional effects on IL-10 secretion.
  
  
  OBJECTIVE
  To test the hypothesis that IL-10 promoter region polymorphisms are associated with susceptibility to ALD.
  
  
  METHODS
  The allele frequencies for the two single base pair substitutions at positions -627 (C-->A) and -1117 (A-->G) in the IL-10 promoter were determined in 287 heavy drinkers with biopsy proved advanced ALD, 107 heavy drinkers with no evidence of liver disease or steatosis only on biopsy, and 227 local healthy volunteers.
  
  
  RESULTS
  At position -627, 50% of patients with advanced ALD had a least one A allele compared with 33% of controls (p<0.0001) and 34% of drinkers with no or mild disease (p=0.017). At position -1117, the slight excess of the A allele in drinkers with advanced disease was because of linkage disequilibrium between the A alleles at the two sites.
  
  
  CONCLUSIONS
  Among heavy drinkers, possession of the A allele at position -627 in the IL-10 promoter is associated with an increased risk of advanced liver disease. This is consistent with recent functional data that the -627*A allele is associated with low IL-10 expression which will favour inflammatory, immune mediated, and profibrotic mechanisms of alcohol related liver injury.
authors.affiliation: Centre for Liver Research, University of Newcastle, Newcastle-upon-Tyne, UK.
authors.forename: J
authors.initials: J
authors.lastname: Grove
authors.forename: A K
authors.initials: AK
authors.lastname: Daly
authors.forename: M F
authors.initials: MF
authors.lastname: Bassendine
authors.forename: E
authors.initials: E
authors.lastname: Gilvarry
authors.forename: C P
authors.initials: CP
authors.lastname: Day
mesh_terms: D000483:Alleles; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics*; D008104:Liver Cirrhosis, Alcoholic / Q000235:genetics*; D008297:Male; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic
chemical_list: D016753:Interleukin-10