Gene Could Point to Crohn's, Colitis Treatments

Variant helps protect people from the bowel disorders, experts say

THURSDAY, Oct. 26, 2006 (HealthDay News) -- A newly discovered gene may help protect carriers against Crohn's disease and colitis, inflammatory bowel diseases (IBDs) that affect an estimated one million Americans, researchers say.

The gene produces a protein that's key to a cellular receptor for interleukin-23 (IL-23), a protein involved in the body's inflammatory processes, explains a report published in the Oct. 27 issue of Science.

"We're pleased about the finding because the IL-23 pathway is already known to be important in inflammatory conditions such as asthma," said lead researcher Dr. Richard H. Duerr, associate professor of medicine and human genetics at the University of Pittsburgh. "We were surprised because the most common variant of the gene provides protection. If we could understand what the protective variant is doing and how it affects downstream events, we could find ways to treat or prevent IBD."

The study was funded by the U.S. National Institutes of Health.

The finding is intriguing, said co-researcher Dr. Judy H. Cho, since most research into disease-linked genes find variants that boost the carrier's risk for the illness.

But in this case, "instead of looking at the genetics of disease we're looking at the genetics of health," said Cho, who is associate professor of medicine and genetics at Yale University School of Medicine

It is "a potentially important discovery" because it might be quickly translated into treatment, added Dr. John Braun, chairman of pathology and medicine at the University of California, Los Angeles. Braun is also chairman of the national scientific advisory committee of the Crohn's amp; Colitis Foundation of America.

There's an added plus to the finding: While other genes associated with IBD have been identified, "so far, none of those genes have drugs that are directly known to affect them," Braun said. But, "in this case, drugs are already available that act on the IL-23 system."

A number of drugs in various stages of development are being tested against IL-23-related conditions, including psoriasis, rheumatoid arthritis and multiple sclerosis, he said.

"The reason why this is such a nice finding is that the human genetics correspond with [the] immunology," Cho said. "This inflammatory pathway is typical of not only intestinal problems but also of others, like rheumatoid arthritis and psoriasis."

The IL-23 pathway is important in the body's infection defense system, Cho said. IBD appears to be caused by an abnormal reaction against the very high concentration of bacteria normally found in the intestines. Thus, it might be possible "to block IL-23 function in a way that markedly reduces disease," she said.

But it's also necessary to tread cautiously, Duerr said, because the IL-23 pathway also helps fight infection. "Acting on the variant that is protective in IBD might worsen other disorders," he warned. "We have to understand what the variant is doing in the IL-23 pathway."

The discovery was made by systematically scanning all of the 22,000 genes in the human genome, looking for variants present in persons with Crohn's disease but not in healthy individuals.

The scan detected two variants in one gene already associated with IBD, CARD15. The only other association was found in variants of the IL-23 gene. When the researchers looked closely at the gene, they found several variants associated with increased risk of IBD. But one appeared to confer very strong protection against IBD.

"One of every six or seven Caucasians are carriers of the protective allele [variant]," Cho said. "If you have one copy of the protective allele, you are two to four times less likely to develop Crohn's disease."

The low incidence of the protective variant is unusual, Duerr said. "Almost always, a good variant will have an increased frequency in the population," he said.

More information

For more on Crohn's disease and related conditions, consult the Crohn's amp; Colitis Foundation of America.

SOURCES: Richard H. Duerr, M.D., associate professor, medicine and human genetics, University of Pittsburgh; John Braun, M.D., chairman of pathology, University of California, Los Angeles; Judy H. Cho, associate professor, medicine and genetics, Yale University School of Medicine, New Haven, Conn; Oct. 27, 2006 Science
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