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Genes Regulating Interleukin Linked to Biliary Cirrhosis

Study identifies variant genes implicating Interleukin-12 signaling in primary biliary cirrhosis

WEDNESDAY, May 20 (HealthDay News) -- Primary biliary cirrhosis may be linked to variants in the genes that regulate interleukin-12 signaling in the immune response, according to a study reported in the May 21 issue if the New England Journal of Medicine.

Gideon M. Hirschfield, Ph.D., of the University of Toronto, and colleagues conducted genome analysis on DNA samples from 2,072 Canadian and United States' subjects to identify the genetic loci associated with primary biliary cirrhosis, a disease known to have a genetic component. The study group included 536 subjects with cirrhosis and a control group of 1,536 without the disease. The researchers genotyped over 300,000 single-nucleotide polymorphisms, ultimately completing fine-mapping studies on loci thought to be associated with the disease.

The researchers identified 13 loci across the HLA class II region with significant association to primary biliary cirrhosis, including the HL-DQB1 locus, which had the strongest association (odds ratio, 1.75 in comparison with the control group). Two other significant associations were identified at the IL12A locus that encodes interleukin (odds ratio, 1.54, for both) and one at the IL12RB2 locus (odds ratio, 1.51). The fine-mapping studies identified a five-allele haplotype in the region flanking IL12A associated with the disease.

"Our data show significant associations between primary biliary cirrhosis and common genetic variants at the HLA class II, IL12A and IL12RB2 loci and suggest that the interleukin-12 immunoregulatory signaling axis is relevant to the pathophysiology of primary biliary cirrhosis," the authors write.

Several of the study authors reported receiving financial support from the pharmaceutical industry.

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