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Scientists identify genetic mutations associated with prognosis in Crohn's disease


View:48 Time:2017-01-10


Crohn's disease is a disease with a complex cause and pathogenesis. It is not caused by one single gene but by multiple genes. So far, scientists have identified as many as 170 genetic mutations that increase the risk of the complex disorder. In traditional perspective, a person who has enough of these mutations will develop Crohn's disease. And the number of the mutations a person has correlates with the severity of the illness. But a new study appearing in Nature Genetics now challenges this view.

The study, conducted by researchers from University of Cambridge, University of Otago, Newcastle University and many other universities and institutes, shows that genetic mutations that impact the progression or prognosis of Crohn's disease are not the same as those that elevate the risk of Crohn's disease.

The researchers noted that earlier studies have found many genetic risk factors for Crohn's disease, but have not revealed why some people develop severe disease while others only have mild symptoms. There is evidence that Crohn's disease patients of the same family may see it progress in a similar way, supporting a genetic contribution to prognosis.

For this work, lead researcher Kenneth Smith and colleagues performed a genome-wide association study on patients with either very mild or very serious Crohn's disease. They identified four genetic variants associated with disease severity, none of which is associated with disease susceptibility -- the risk of developing a disease. The four genetic variants were in or close to the following genes: FOXO3, IGFBP1, MHC and XACT.

In the next step, Smith's team investigated genetic mutations known to increase the risk of Crohn's disease, and discovered that all these mutations do not impact disease severity. Collectively, the study showed that the genetic contribution to prognosis in Crohn's disease is different to the genetic contribution to disease susceptibility. This could lead to a deeper understanding of how Crohn's disease progresses in individual patients, and could provide new treatment strategies for this complex disease.

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