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Gene Discovery Gives Clues to Crohn's Disease, Colitis
Date:11/4/2009

Mutation is tied to a protein implicated in rare form of bowel disorder, researchers say

WEDNESDAY, Nov. 4 (HealthDay News) -- People with painful, chronic bowel conditions such as Crohn's disease and ulcerative colitis could see a glimmer of hope from new research.

Scientists say they've spotted a genetic flaw that could drive a rare childhood form of colitis, and the finding might have implications for the broader range of illnesses collectively known as inflammatory bowel disease (IBD).

Genetic analysis of nine children with a severe form of early-onset colitis found mutations of two genes producing cell receptors for interleukin-10, a protein that controls the body's inflammatory response, according to a report published online Nov. 4 in the New England Journal of Medicine.

In one case, a bone marrow transplant eliminated a child's disease, the report said.

About one million Americans have been diagnosed with IBD, which includes ulcerative colitis and Crohn's disease. These conditions involve a persistent inflammation of the intestinal tract that can cause bouts of diarrhea, rectal bleeding and other symptoms.

The study is not the first to link interleukin-10 with IBD, noted study researcher Alejandro A. Schaffer, a staff scientist at the U.S. National Center for Biotechnology Information. Previous animal and human studies led to trials of interleukin-10 treatment for IBD patients that were not successful, he said.

But the new study shows that "there may be some subsets of adult patients who have insufficient amounts of interleukin-10," Schaffer said. "We are suggesting that there might be a subset of patients worth identifying and treating differently."

It's not now possible to say how large that subset might be, he said.

"We're very excited about this discovery," said study lead author Dr. Erik-Oliver Glocker, a postdoctoral researcher at University College London in the United Kingdom.

The study, done at centers in Germany, the United Kingdom and the United States, identified two mutated genes for the molecules that allow interleukin-10 to act on cells. "These mutations have very severe consequences," Glocker said. "If you have a mutation in the receptor, interleukin-10 doesn't work and the entire immune system is off-balance."

It took a lot of screening to find young people with this specific genetic flaw, Glocker said. The disease usually emerges later in life, and "in older patients, it could be different," he said.

"There have been a lot of different genetic studies of Crohn's disease, and they have always found genes that might be concerned," Glocker said. "Maybe we can screen adult patients for the genes we have described and think of a similar treatment. If you have this mutation, you might be suitable for a bone marrow transplant."

But adult IBD is a complex condition, genetically speaking, he added.

"The problem is that in Crohn's disease patients, the cause of the disease is not well understood," Glocker said. "In the patients we had, we know the genes and the functions of the genes and the proteins. And that makes treatment -- a bone marrow transplant -- much easier. We're not sure that a transplant should be considered in adult Crohn's patients."

A number of variants of other genes have been detected in people with IBD, Schaffer said. "We're not saying anything about those patients, unless they also have the interleukin-10 variant," he said.

More information

There's more on IBD and its treatment at the American College of Gastroenterology.



SOURCES: Alejandro A. Schaffer, Ph.D., staff scientist, U.S. National Center for Biotechnology Information, Bethesda, Md.; Erik-Oliver Glocker, M.D., postdoctoral researcher, University College London, U.K.; Nov. 4, 2009, New England Journal of Medicine, online


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