In the current study, Brant's team focused on the NFKB1 gene, which in addition to IBD, may have a role in a variety of diseases including cancer, AIDS, asthma, arthritis, shock, lung disease, diabetes, atherosclerosis and stroke. A major clue that NFKB1 may be involved in IBD was uncovered when it was shown that NFKB1 seems to be responsible for mice genetically predisposed to developing colitis, says Brant.

The team searched the DNA of 235 families with IBD (from Johns Hopkins, the University of Chicago and the University of Pittsburgh) in which 131 had offspring with ulcerative colitis for evidence of a link between the disease and the NFKB1 gene. They found six variants of the gene, and showed that one variant - involving a small deletion of the NFKB1 gene sequence - influences the amount of NFKB1 gene product made. Closely examining the pedigrees with several genetic techniques revealed that this NFKB1 deletion variant was significantly increased in the 131 ulcerative colitis offspring, and thus strongly suggested a link between the gene variant and ulcerative colitis. They then replicated this finding in a second, independent set of patients (including those from University of Toronto) with ulcerative colitis. The researchers suggested that this NFKB1 deletion may potentially be important in the some of the many other diseases where NFKB1 has been shown to play a role.

In the second study, appearing in the December 2003 issue of the American Journal of Human Genetics and led jointly by Brant and Judy Cho, M.D., of the University of Chicago, they found that a version of another gene, called MDR1, is strongly associated with Crohn's disease and possibly ulcerative colitis as well.

The DNA of 1,118 individuals, including 558 patients with IBD and 329 families in which at least one person had t
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Contact: Trent Stockton
tstockt1@jhmi.edu
410-955-8665
Johns Hopkins Medical Institutions
19-Dec-2003