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you are here: DentalPlans.com > Dental Health Articles > Research > Crohns Disease Gene Identified
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Updated: 10/31/2006 11:08:49 AM |
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Alterations in the receptor for a known inflammatory response pathway are strongly associated with Crohn's disease and ulcerative colitis, according to a report by a consortium of American and Canadian researchers in the October 26 online Science Express.
Crohn's disease and ulcerative colitis, collectively called inflammatory bowel disease (IBD), are chronic disorders that cause abdominal pain, diarrhea and gastrointestinal bleeding and affect over one million Americans. Because IBD tends to run in families and is more frequent in certain ethnic populations, especially Ashkenazi Jews, scientists have long suspected a significant genetic component.
According to senior author Judy H. Cho, M.D., associate professor in the Departments of Medicine and Genetics at Yale School of Medicine, the team found that mutations in a receptor gene associated with the interleukin-23 (IL-23) pathway, are linked to Crohn's disease. The IL-23 pathway is known to target organ-specific inflammatory responses.
"This finding is particularly intriguing because we appear to have identified a gene variant that protects against development of IBD," said Cho, who also directs the Inflammatory Bowel Disease Center at Yale. "It causes us to think about the genetics of health as well as about the genetics of the disease. One mutation appears to offer significant protection from IBD, and will be a crucial target for drugs that might better manage Crohn's disease and ulcerative colitis."
Previous genetic studies found a link between Crohn's disease and mutations in a gene known as CARD 15, but those mutations alone did not account for all of the genetic components of the disease.
To identify additional genes associated with IBD, the international research team scanned the genome, testing more than 300,000 single nucleotide polymorphisms, or SNPs, in people with Crohn's disease. They compared results with the SNPs in a similar number of people without IBD. In addition to two differences in the CARD 15 gene, they found a third variant SNP, which was in a different gene on a different chromosome-the interleukin-23 receptor.
"We know that the IL-23 receptor plays an important role in activating inflammation, including in organs of the digestive tract, therefore it could be an extremely important target for improving the management of Crohn's disease and ulcerative colitis," said Cho. "However, the IL-23 pathway may serve a useful purpose in protecting us from other diseases, so when seeking to block or manipulate its activity with drugs or other means, we need to take this balancing act into consideration."
Cho and co-authors represent the IBD Genetics Consortium, which is funded by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health (NIH). Cho said large study sizes made possible by the consortium offer more definitive conclusions.
"This important discovery not only offers new hope for better therapies for patients with Crohn's disease, it also highlights the promise of the human genome project and subsequent investments by the NIH in large scale, collaborative research projects to unravel the causes of, and hopefully better treatments for complex, enigmatic diseases," said Stephen P. James, M.D., director of the Division of Digestive Diseases and Nutrition at the National Institutes of Health's NIDDK.
The consortium's member institutions include Cedars-Sinai Medical Center in Los Angeles, the University of Chicago, Johns Hopkins University, Université de Montréal, the University of Pittsburgh, the University of Toronto, and Yale School of Medicine.
© 2006 HealthNewsDigest.com
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