NO EVIDENCE FOR INVOLVEMENT OF THE INTERLEUKIN-10 -592-PROMOTER POLYMORPHISM IN GENETIC SUSCEPTIBILITY TO PRIMARY BILIARY-CIRRHOSIS

Background/Aims: Primary biliary cirrhosis is a chronic cholestatic li ver disease with an autoimmune aetiology, Family studies, which have s hown a significantly increased incidence of primary biliary cirrhosis in the close relatives of patients, suggest that genetic factors play a significant role in determining disease susceptibility, Several stud ies have previously identified loci which appear to play a role in det ermining this susceptibility, including the MHC class II allele HLA DR 8, and the class III encoded C4A null allele (C4AQ0). Here, we have st udied another candidate susceptibility locus in primary biliary cirrho sis, an apparently functional biallelic polymorphism at position -592 in the promoter region of the gene encoding the immuno-modulatory cyto kine interleukin-10, Interleukin-10 plays an important role in the fun ctional control, in vivo, of autoreactive Th-1 type CD4+ T-cells, with experimental manipulation of interleukin-10 leading to significant mo dulation of disease development in animal models of autoimmunity, Meth ods: Interleukin-10 -592 genotypes were studied by polymerase chain re action in 171 well-characterised, histologically-staged, primary bilia ry cirrhosis patients and 141 locally matched controls, Results: Of 17 1 primary biliary cirrhosis patients, 99 were homozygous for the commo ner allele (C/C), 68/171 (40%) were heterozygotes (A/C), whilst 4/171 (2%) were homozygous for the rarer allele (A/A), These genotype freque ncies were not significantly different from those seen in controls (p= 0.49, odds ratio 1.2 [0.8-1.9]). Conclusions: These findings, in the f irst study of IL-10 as a candidate locus in a human autoimmune disease , suggest that IL-10 -592 is not a susceptibility locus in primary bil iary cirrhosis.