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Team pinpoints amino acid variation in immune response gene linked with ulcerative colitis
Date:12/15/2011

PITTSBURGH, Dec. 15 The association between the inflammatory bowel disease ulcerative colitis and a gene that makes certain cell surface proteins has been pinpointed to a variant amino acid in a crucial binding site that profoundly influences immune response to antigens, including gut bacteria, reports a team of researchers at the University of Pittsburgh, Cleveland Clinic, Carnegie Mellon University and Harvard Medical School. They published the findings today in the online version of Genes & Immunity.

Variations in genes that regulate immune responses in a region of chromosome 6 have long been linked with susceptibility for many infectious and chronic inflammatory conditions, including ulcerative colitis, said Richard H. Duerr, M.D., professor of medicine, Pitt School of Medicine, co-director and scientific director, UPMC Inflammatory Bowel Disease Center, and the corresponding author of the study. Ulcerative colitis is characterized by recurrent inflammation of the large intestine that results in diarrhea mixed with blood and abdominal pain.

"We tested more than 10,000 points, called single nucleotide polymorphisms, or SNPs, in the gene sequence in this chromosomal region, and we also tested amino acid variations in human leukocyte antigen (HLA) proteins that were deduced from the SNPs to identify those most important for ulcerative colitis," Dr. Duerr said. "Refining the gene association signals in this region enabled us to better understand the underlying mechanisms of the disease."

Using sophisticated association techniques, the authors confirmed that an HLA gene called DRB1, which codes for a protein that is involved in the immune response and routinely tested in tissue matching for organ transplantation, was uniquely related to ulcerative colitis. Variation, or polymorphism, in that gene altered which amino acid was selected for the 11th position in the DRB1 protein a key location because it is in a pocket of the so
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Contact: Anita Srikameswaran
SrikamAV@upmc.edu
412-578-9193
University of Pittsburgh Schools of the Health Sciences
Source:Eurekalert

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