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Apr 17, 2007

Researchers Discover Genes Associated with Crohn’s Disease

  • A search of the entire human genome revealed three genes linked to increase the risk of developing nflammatory bowel disease. Additionally, the study identified two regions of the genome where genetic risk factors are located but no known genes were implicated.

    The researchers found that PHOX2B, NCF4, and ATG16L1 constitute genetic risk factors for Crohn's disease or colitis as well as numerous biological pathways not previously thought to play a role in Crohn's disease.

    "The identification of the PHOX2B gene in this study may implicate a role for neuroendocrine cells of the intestinal epithelium as having a role to play in Crohn's Disease,” reports John D. Rioux, Ph.D., associate professor of medicine at the Montreal Heart Institute and the Universite de Montreal.

    “In addition, the identification of the NCF4 gene indicates that altered reactive oxygen species production, important in the generation of an effective antimicrobial response, may lead to increased risk of developing the disease.”

    The fact that the authors also found strong association of the ATG16L1 gene provides further evidence that an individual's response to microbes has an influence on susceptibility to Crohn's disease.

    In addition to demonstrating its association to the disease, the authors found that ATG16L1 is essential for the normal autophagic process used to degrade worn-out cellular components and help eliminate some pathogenic bacteria. "We propose that genetic variation in the ATG16L1 gene leads to alterations in how the body uses autophagy and therefore may result in increased persistence of both cellular and bacterial components, leading to inappropriate immune activation and increased risk of Crohn's disease" adds Dr. Rioux.

    The report appears in the April 15 online edition of Nature Genetics.



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