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Los Angeles (California) [US], April 23 : A genetic variation uncovered by Cedars-Sinai researchers increases the likelihood of getting perianal Crohn's disease, the most devastating type of Crohn's disease.The variation alters the body's recognition and handling of bacteria, making it less effective at fighting illnesses.UT, a peer-reviewed journal, reported the findings."Fistulizing perianal Crohn's disease can be a really miserable condition," said co-senior author Dermot McGovern, MD, PhD, director of Translational Research in the Cedars-Sinai F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute and the Joshua L. and Lisa Z. Greer Chair in Inflammatory Bowel Disease Genetics. We can begin to create novel treatment techniques for patients identified with this chronic inflammatory disorder, most of whom currently require surgery and many require several surgeries, by learning more about the underlying reasons."Perianal Crohn's disease is a complication of Crohn's disease, a chronic inflammatory disorder that affects the digestive tract. The complication causes inflammation and ulceration of the skin around the anus, as well as other structures in the perianal area. Perianal Crohn's disease occurs in up to 40% of people with Crohn's disease and has limited treatment responses, resulting in a poor quality of life."We have become much more successful in identifying genetic variants associated with the risk of developing diseases, but what we did here is specifically focused on a very complicated and severe mfestation of Crohn's disease. And that's an unusual approach in genetic research," said Talin Haritunians, PhD, a research assistant professor who is part of the McGovern Laboratory and co-first author of the study.To discover genetic variants with a direct tie to this severe mfestation, investigators analyzed genetic data from three independent cohorts of patients with Crohn's disease. The groups included a Cedars-Sinai cohort, an international genetics cohort recruited from over 20 countries, and a cohort recruited from seven academic research medical centres throughout the United States. The three groups totalled 4,000 patients with perianal Crohn's disease and more than 11,000 Crohn's disease patients without this complication.The team of scientists compared the cohorts to see if they could detect genetic loci, which are areas of the genome associated with developing this mfestation.The team identified 10 novel genetic loci and 14 known inflammatory bowel disease loci to be associated with the development of perianal complications.During the functional characterization analysis, the team focused on a single change in a specific gene, called an SNP, that was associated with perianal Crohn's Disease. This genetic variant affects a protein called Complement Factor B (CFB), which leads to a loss of function of this protein that is important for fighting infections, which may be why patients with this genetic change are more likely to have the condition.The investigators performed multiple analyses to confirm that there really is a loss of function in CFB, which can have a dramatic impact on the body."In the case where you have this mutation that leads to a nonfunctional protein, you don't get the normal signalling cascade, and the body doesn't recognize the bacteria as being harmful, and thus those bacteria are not eliminated," said co-senior author of the study Kathrin Michelsen, PhD, a research assistant professor of Medicine and Biomedical Sciences at Cedars-Sinai, adding, "So, for those patients who have perianal Crohn's disease, there are connections that form from the rectum to the skin area. And those tunnels are full of bacteria that are not being eliminated."Michelsen also noted the study demonstrates an important role for the alternative complement pathway and CFB in the development of perianal Crohn's disease. The findings also suggest that targeting the alternative complement pathway may be a novel therapeutic approach for treating this disabling mfestation of Crohn's disease.This genetic variant can also be associated with other diseases."These genetic variants often predispose to more than one condition, and we believe this discovery potentially has ramifications for other diseases as well, not just Crohn's disease," said McGovern.Disclaimer: This post has been auto-published from an agency feed without any modifications to the text and has not been reviewed by an editor

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