Study Identifies a Gene for Inflammatory Bowel Disease

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In a multicenter study aimed at identifying genetic factors that might contribute to inflammatory bowel disease (IBD), researchers led by Dr Richard H. Duerr, Associate Professor of Medicine at the University of Pittsburgh, and Dr Judy Cho, Associate Professor of Medicine at Yale University compared the genomes of Crohn’s disease patients of European descent, both Jewish and non-Jewish, to those of healthy controls of the same ancestries. More than 1900 subjects were involved in the analysis. The report appears online in the October 26 issue of Sciencexpress (available at: www.sciencexpress.org).

The researchers examined >300,000 single nucleotide polymorphisms, the variations that occur when a nucleotide, a molecular subunit of DNA is altered. “We found a highly significant association between Crohn’s disease and the IL23R gene on chromosome 1p31, which encodes a subunit of the receptor for the pro-inflammatory cytokine interleukin-23,” the authors state. This association was also found in patients with ulcerative colitis.

The study notes that the interleukin (IL)-23 receptor gene is not the only one thought to be associated with IBD, but it seems an especially good candidate. The IL-23 immune pathway was already implicated in IBD, psoriasis, rheumatoid arthritis, and multiple sclerosis. Animal models offer further evidence. Mice genetically engineered to express a subunit of IL-23 suffer severe systemic inflammation, including in the small and large intestines.

The researchers discovered a coding variant—a glutamine allele—that apparently protects against IBD, because it is found less frequently in patients than in healthy controls. “Our discovery of an uncommon allele, or conversely, a very common predisposing allele, reflects a major theme in complex genetics; namely, that functional genetic variation confers a continuum of susceptibility, neutral and protective effects. Furthermore, alleles conferring protection against one disease may result in increased risk for another,” the authors state. “These results and previous studies on the pro-inflammatory role of IL-23 prioritize this signaling pathway as a therapeutic target in inflammatory bowel disease,” the report concludes.