Interleukin 10 promoter region polymorphisms and susceptibility to advanced alcoholic liver disease

Background-The factors determining why less than 10% of heavy drinkers deve lop 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,andanti-fibrotic functions. Several poly morphisms have been identified in the IL-IO promoter and recent evidence su ggests that some of these may have functional effects on IL-10 secretion. Aims-To test the hypothesis that IL-10 promoter region polymorphisms are as sociated with susceptibility to ALD. Methods allele frequencies for the two single base pair substitutions at po sitions -627 (C-->A) and -1117 (A-->G) in the IL-IO promoter were determine d 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 loc al 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 disequili brium between the A alleles at the two sites, Conclusions-Among heavy drinkers, possession of the A allele at position -6 27 in the IL-10 promoter is associated with an increased risk of advanced l iver disease. This is consistent with recent functional data that the -627* A allele is associated with Lour IL-10 expression which will favour inflamm atory, immune mediated, and profibrotic mechanisms of alcohol related liver injury.