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The newspaper of The Johns Hopkins University April 28, 2008 | Vol. 37 No. 32
Multicenter Study Suggests New Genetic Markers for Crohn's

Results shed light on genetic vulnerabilities of Ashkenazi Jews

By Eric Vohr
Johns Hopkins Medicine

What is believed to be the largest study of its kind for the genetic roots of inflammatory bowel diseases has suggested new links to Crohn's disease as well as further evidence that some people of Jewish descent are more likely to develop it.

The study examined changes in DNA associated with the two most common forms of inflammatory bowel disease: Crohn's disease, which is most frequently marked by inflammation of the final section of the small bowel (ileum) and parts of the colon, and ulcerative colitis, an inflammation of the internal lining of the rectum and colon.

Results of the study, published in the March edition of Genes and Immunity, included information gleaned from 993 families with inflammatory bowel disease, or IBD, 244 of whom were Ashkenazi Jews. Up to 30 percent of people with IBD in the United States are estimated to have a family history of the condition, and about 25 percent of these families have both Crohn's disease and ulcerative colitis in the family. People of Ashkenazi Jewish descent are at least twice as likely to develop a form of IBD and are more likely to have familial disease.

"This increased risk for some Jewish people makes our study and results especially significant since this is the first sample size of Jewish families, 244, that was large enough to identify novel gene regions for familial predisposition in this ethnic group," said Johns Hopkins gastroenterologist and genetic investigator Steven R. Brant, senior author of the study and an associate professor in the School of Medicine.

By analyzing common DNA variations known as single nucleotide polymorphisms, or SNPs, the team found evidence for genes causing familial Crohn's disease in the study population specific to Ashkenazi Jewish families with Crohn's disease on previously identified areas of chromosomes 1 and 3. They also identified a never-before-identified region of chromosome 13 that was shared by both Jewish and non-Jewish families with Crohn's disease. Evidence for chromosomal regions that may be linked to ulcerative colitis on chromosomes 2 and 19 for Jewish and non-Jewish families was also noted, according to Brant.

"What makes these results especially significant is not only the large sample size but also the method we used for screening, namely the use of a high-density, single-nucleotide polymorphism genomewide linkage process," Brant said, adding that the new process is 10 times faster than older methods at searching the number of variations across the genome.

Up to now, Brant says, no gene regions implicated in inflammatory bowel disease were specific to Ashkenazi families, and genetic evidence pointing to why Ashkenazi Jews are twice as likely to get the disorder was lacking. The two genetic regions identified on chromosomes 1 and 3 were specific to Ashkenazi Crohn's disease and unrelated to known inflammatory bowel disease genes.

Although further study is needed to narrow down which specific genes are the major players, Brant says it's already clear that the researchers are in the right "neighborhood" to search for IBD/Crohn's disease susceptibility genes.

The National Institute of Diabetes and Digestive and Kidney Diseases Inflammatory Bowel Diseases Genetics Consortium (NIDDK-IBDGC) that organized the study is a multicenter team of American and Canadian investigators established in 2002 to examine genetic links among IBD pedigrees.

The subjects were recruited through the six inflammatory bowel disease genetic research centers of the NIDDK-IBDGC — Cedars-Sinai Hospital in Los Angeles, The Johns Hopkins Hospital and the universities of Chicago, Montreal, Pittsburgh and Toronto.

Genotyping was performed at the SNP Center at the Center for Inherited Disease Research in Baltimore.

The study was funded by the NIDDK branch of the National Institutes of Health. Other researchers who worked on this study include lead author Yin Shugart, of the Johns Hopkins Bloomberg School of Public Health; co-senior author Judy H. Cho, Yale University School of Medicine; and additional researchers, in the United States, from the University of Pittsburgh, Cedars-Sinai Medical Center, The Johns Hopkins University and University of Chicago; and, in Canada, McGill University and the universities of Toronto, Manitoba, Sherbrooke Hospital and Montreal.


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