Genetic links discovered for Crohn's disease

The risk of developing Crohn's disease, a debilitating inflammatory ailment,has beenlinked to seven genes, Canadian and U.S. researchers say.

More than 150,000 Canadians have Crohn's disease, which can affect any part of the gastrointestinal tract and cause inflammation in bowel tissue. Drugs or surgery do not cure it, but may relieve the symptoms of severe stomach pains, diarrhea and trouble eating.

Crohn's and a similar condition called ulcerative colitis are collectively known as inflammatory bowel disease or IBD.

In this week's issue of the journal Nature Genetics, John Rioux of the Montreal Heart Institute and the University of Montreal and his colleagues said seven genes are associated with the disease, including four that have been newly identified.

Identifying genes that predispose people to Crohn's diseasemay helpprovide insight into the causes of the disease, which could lead to new ways to treat it in the long term, the researchers said.

"The multiple genetic risk factors we've identified provide important targets for current functional studies aimed at understanding the disease and important targets for drug development to improve therapy of Crohn's disease in the future," said Dr. Steven Brunt, a senior co-author of the study and a gastroenterologist at Johns Hopkins University in Baltimore, Md.

Given that IBD tends to run in families and is more common in certain ethnic populations such as Ashkenazi Jews, researchers suspected genetic links in the disease, along with environmental factors such as smoking.

Microbial role

For the study, the team used data from the Human Genome Project, a map of human DNA, to scan the genomes of about 6,000 people. Half of the people had Crohn's and rest were healthy controls.

About 300,000 tiny genetic variants called single nucleotide polymorphisms, or SNPs, were assessed to identify the four new risk factors: PHOX2B, NCF4, FAM92B, and a region on chromosome 10.

Scientists suspect that an inappropriate response to bacteria in our digestive system somehow causes the immune system to attack the lining of the digestive tract in Crohn's, leading to inflammation.

The discovery of NCF4 indicates that changesin the production offree radicals, which are needed for an effectiveimmune response againstbacteria, may also lead to an increased risk of Crohn's, said Rioux.

Identificationof the PHOX2B gene may implicate a role for neuroendocrine cells of the intestinal lining, added study co-author author Dr. Mark Silverberg, a professor of medicine and surgery at the University of Toronto.

The study also provides more evidence that a variation in a gene previously linked to Crohn's, called ATG16L1, is needed for autophagy— the process used to break downworn-out parts of cells and help eliminatepathogenic bacteria, Rioux said.

The findings were tested and confirmed in two othersets of patients and controls.