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A pair of discoveries helps unravel complex genetics of inflammatory bowel disease

Researchers at Johns Hopkins have linked versions of two different genes with the inflammatory bowel diseases known as Crohn's disease and ulcerative colitis. The discoveries are a crucial step in developing new treatments and prevention strategies for these disabling conditions that together afflict one million Americans, the scientists say.

The first discovery demonstrates that a version of the NFKB1 gene was an important risk factor for ulcerative colitis. NFKB1 is the gene that contains the DNA sequence for nuclear factor kappa B (NF-Kappa B) protein, which is one of the foremost regulators of the immune system and programmed cell death. The results are reported in the January 1, 2004 issue of the journal Human Molecular Genetics.

"Our greatest hope is that by identifying the gene abnormalities associated with inflammatory bowel disease (IBD), we'll be able to figure out how they contribute to causing disease and then interfere with that process to stop the disease in its tracks," says Steven Brant, M.D., associate professor of medicine at Johns Hopkins, director of the Meyerhoff Inflammatory Bowel Disease Genetics Laboratory, whose research team discovered the NFKB1 link.

Evidence from twin studies and the tendency for IBD to run in families strongly suggested a genetic component to the disease, says Brant. Relatives of Crohn's disease patients have a 10-fold risk of developing Crohn's disease, while relatives of ulcerative colitis patients have an eightfold risk of developing ulcerative colitis. In addition, the two diseases appear to be genetically related to each other, as relatives of patients with just one of the diseases have an increased risk of developing either Crohn's or ulcerative colitis.

For these reasons, Brant and colleagues have been searching for genes that might contribute to the development of IBD and, in 2001, they participated in the discovery of the first gene, called NOD2, that was clearly associated wi
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Contact: Trent Stockton
tstockt1@jhmi.edu
410-955-8665
Johns Hopkins Medical Institutions
19-Dec-2003


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