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Medicineworld.org: Gene Target Against Crohn's Disease And Ulcerative Colitis

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Gene Target Against Crohn's Disease And Ulcerative Colitis

Gene Target Against Crohn's Disease And Ulcerative Colitis
The discovery by a six-member Inflammatory Bowel Disease (IBD) Genetics Consortium of a genetic risk factor for IBD has been reported in Science Express, the online publication of the journal Science. As per one of the Canadian principal investigators, director of the Laboratory in Genetics and Genomic Medicine of Inflammation at the Montreal Heart Institute, Dr. John D. Rioux, "This discovery may lead to a paradigm shift in our thinking from 'genetics of diseases to genetics of health', especially as concerns Crohn's Disease and Ulcerative Colitis." This discovery was, in part, due to the contributions of the gastroenterologists of the Quebec IBD Genetics Consortium led by Dr. Rioux and Dr. Alain Bitton of the McGill University Health Centre.

Inflammatory bowel disease, or IBD, describes two similar yet distinct conditions called Crohn's disease and ulcerative colitis. These diseases affect the digestive system and cause the intestinal tissue to become inflamed, form sores and bleed easily. Symptoms include abdominal pain, cramping, fatigue and diarrhea.

Crohn's disease may affect the gastrointestinal tract, from the mouth to the anus, and while Crohn's disease can not be cured by drugs or surgery, either may relieve symptoms.

In Canada, an estimated 170,000 Canadian men and women suffer from IBD, most frequently between the ages of 15-25, or 45-55. It is especially difficult for children and young adults since it often affects a person's self-concept. IBD is found throughout the world. However, it appears to be most common in North America and northern Europe; Canada having one of the highest incidence rates of IBD in the world. (1) In the U.S., more than 1 million Americans have Crohn's or colitis.

Since IBD tends to run in families and is more frequent in certain populations, particularly Ashkenazi Jews, researchers have long suspected a significant genetic component. Eventhough prior genetic studies found a link between Crohn's disease and mutations in a gene known as CARD15, those mutations alone are not considered to account for the entire genetic component of disease.

As per senior author Judy H. Cho, M.D., associate professor in the departments of Medicine and Genetics at Yale School of Medicine, the findings highlight a major inflammatory pathway and may change our thinking about disease-associated genetic variation. "This pathway is especially intriguing because we appear to have identified a gene variant that protects against development of IBD," said Dr. Cho, who is also director of the Inflammatory Bowel Disease Center at Yale.

While mutations of the gene which codes for a receptor in a major inflammatory pathway are strongly linked to Crohn's disease, surprisingly, Consortium scientists report that one type of mutation may confer significant protection and identify potential targets for drugs therapies for the management of Crohn's disease and ulcerative colitis.

To identify additional genes that are linked to IBD, the international team of scientists scanned the genome some 22,000 by testing more than 300,000 nucleotide polymorphisms, or SNPs, in people with Crohn's disease, and a similar number of people without IBD. The scan led to an unexpected discovery.

Eventhough several polymorphisms were linked to a significantly increased risk of developing IBD, one appeared to confer a very strong protection against IBD.

"Of all the SNPs we studied in people with and without IBD, this protective SNP was the most statistically significant finding in our study. So, it took us a bit by surprise," said first author, Richard H. Duerr, M.D., associate professor of medicine and human genetics, University of Pittsburgh. "What it means in terms of improving therapys for IBD patients, we are not sure yet".

Nonetheless, members of the Consortium are attempting to tease out the specific downstream effects of this protective polymorphism. Yet, because IL-23 plays an important role in activating inflammation, including in the organs of the digestive tract, it could be an extremely important target for improving the management of Crohn's disease and other IBDs.

"Recent studies in mice in which the gene for IL-23 was deleted demonstrated that it is essential for triggering chronic intestinal inflammation. Such evidence, combined with the current discovery, suggests therapies that target the IL-23 pathway may lead to more individualized, better-directed therapies for IBDs. In fact, blocking the activity of IL-23 or manipulating its pathway may be an effective way to manage IBD," said Dr. Rioux. "I am confident that the future genetic studies by this collaborative group will continue to improve our understanding of these and other chronic inflammatory diseases," he added.


Posted by: Sue    Source




Did you know?
The discovery by a six-member Inflammatory Bowel Disease (IBD) Genetics Consortium of a genetic risk factor for IBD has been reported in Science Express, the online publication of the journal Science. As per one of the Canadian principal investigators, director of the Laboratory in Genetics and Genomic Medicine of Inflammation at the Montreal Heart Institute, Dr. John D. Rioux, "This discovery may lead to a paradigm shift in our thinking from 'genetics of diseases to genetics of health', especially as concerns Crohn's Disease and Ulcerative Colitis." This discovery was, in part, due to the contributions of the gastroenterologists of the Quebec IBD Genetics Consortium led by Dr. Rioux and Dr. Alain Bitton of the McGill University Health Centre.

Medicineworld.org: Gene Target Against Crohn's Disease And Ulcerative Colitis

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