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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