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Gene mutation responsible for Chrohn's disease inflammation identified in Temple study

A mutation in one of the genes that might be responsible for the inflammation that characterizes Crohn's disease has been identified by researchers at Temple University's School of Medicine (TUSM).

Their study, "The mutation Ser511Asn leads to N-glycosulation and increases the cleavage of high molecular weight kininogen in rats genetically susceptible to inflammation," appears in the October 15 issue of Blood (www.bloodjournal.org).

Although the exact cause of Crohn's disease, a digestive disorder afflicting approximately 500,000 adults in the U.S., remains unknown, scientists agree that it is governed by the immune system and has a genetic component.

"Everyone has bacteria throughout their digestive tract, but in people with Crohn's disease, bacterial products activate inflammation, as well as the immune system, which leads to the debilitating symptoms of Crohn's, including diarrhea, constipation and cramps," said Robert Colman, MD, professor of medicine at TUSM and lead investigator of the study. "Since this reaction doesn't occur in everyone, we suspected that there was a genetic component."

While other researchers have found several genes that indicate an increased susceptibility to Crohn's disease, the Temple study went a step further and explored the role of genetics in causing the inflammation that characterizes the disease.

Specifically, Temple researchers identified a genetic mutation that involves one of the proteins (kininogen) known to be involved in inflammation. In a previous study, Colman demonstrated that a deficiency in this protein led to a much milder form of inflammation.

"Finding this mutation is important because we are now in a position to look for the same genetic mutations in humans, the presence of which would confirm that the protein kininogen plays an important role in the origin and development of Crohn's. We could then direct therapy towar
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Contact: Eryn Jelesiewicz
eryn.jelesiewicz@temple.edu
215-707-0730
Temple University
15-Oct-2003


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