A variant of a protein that normally promotes the digestion and clearance of bacteria by cells is associated with elevated risk of Crohn disease, according to a study to be published in the February 2007 issue of Nature Genetics.
Crohn disease in an inflammatory bowel disease that tends to run in families and as such is thought to have a significant genetic component. Jochen Hampe and colleagues chose more than 7,000 genetic variants across the genome that are known to alter the sequence of individual proteins, and assessed their frequencies in several hundred individuals from Germany with the disease. They found a variant of the gene encoding the protein ATG16L1 to be significantly more likely to be present in individuals with Crohn disease than in those who did not have the disease. The result was confirmed in a group from the UK, lending credibility to the finding.
The risk conferred by the ATG16L1 variant was also apparent in individuals who are already known to be at extra risk owing to a variant in the gene CARD15, suggesting that the products of these genes might interact. The fact that ATG16L1 is involved in clearance of bacteria is consistent with the idea that Crohn disease results from inappropriate immune responses to foreign substances.
Jochen Hampe (Christian-Albrechts University, Kiel, Germany)
Abstract available online.
(C) Nature Genetics press release.
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