Genetic Link to Inflammatory Bowel Disease Identified

European study finds mutations affect interleukin-10 signaling

WEDNESDAY, Nov. 4 (HealthDay News) -- Genetic mutations that interfere with interleukin-10 signaling are associated with inflammatory bowel disease, according to a study published online Nov. 4 in the New England Journal of Medicine.

Erik-Oliver Glocker, M.D., of the Royal Free Hospital and University College London, and colleagues identified candidate genes in members of two unrelated families with children affected by early-onset inflammatory bowel disease, and screened for mutations in two candidate genes among six other patients with early-onset colitis.

The researchers found three distinct homozygous mutations in genes IL10RA and IL10RB affecting the interleukin-10 receptor in four out of nine patients with early-onset colitis. Patients deficient in IL10R subunit proteins had increased secretion of pro-inflammatory cytokines, also suggestive of disruption to interleukin-10-induced signaling, the investigators note.

"We have shown that loss-of-function mutations in either IL10RA or IL10RB can be found in children with severe, early-onset enterocolitis, findings that are consistent with the idea that a lack of negative-feedback signaling mediated by interleukin-10 perturbs homeostasis of the intestinal immune system," the authors write. "Since IL10R1 is expressed on many cells of the innate and adaptive immune system, further studies are needed to determine which types of cells are primarily responsible for the altered intestinal immunity."

One author reported financial relationships with pharmaceutical and medical companies.

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Last Updated: November 04, 2009

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