American and other researchers have discovered five new genetic mutations that
make Ashkenazi Jews four times more likely than other populations to develop
The online journal PLoS (Public Library of Science)
reported the discovery in its March 8th issue.
The findings, from a
multicenter study, are the first step in an attempt to explain why Ashkenazi
Jews are at significantly higher risk for the disorder, which is a form of
inflammatory bowel disease (IBD). Crohn’s is an autoimmune condition in which
the immune system attacks healthy tissue in the gastrointestinal track, causing
Crohn’s usually affects the intestines, which are
continually inflamed and thick, but it can occur anywhere from the mouth to the
end of the rectum. In this condition, the body overreacts to normal bacteria in
the intestines While it can occur at any age, the typical ages of onset are
between 15 and 35. People at high risk include smokers, those with a family
history of Crohn’s and Jews of Ashkenazi origin, but until now, the defective
genes had not been identified.
Its main symptoms are fatigue, loss of
appetite, abdominal cramps, pain when passing stool, fever, weight loss,
diarrhea, possibly eye inflammation, joint pain and swelling, swollen gums and
skin ulcers. In addition to a physical exam, tests and scans, a stool culture is
often conducted to rule out other possible causes of the symptoms.
Burrill Crohn first characterized the disease exactly 80 years ago at New York’s
Mount Sinai School of Medicine. Prof. Inga Peter, a geneticist at Mount Sinai,
led the international research team to search for unique genetic risk factors in
Previous studies had identified 71 genetic variants of
Crohn’s disease risk in people, especially Jews of central and eastern European
ancestry. Peter and her team conducted a two-step genome-wide association study
comparing 1,878 Ashkenazi Jews with Crohn’s disease to 4,469 Ashkenazi Jews
without the disease, using DNA samples to evaluate their genetic make-up. The
research team found 12 of the known risk variants, but also discovered five new
genetic risk regions on chromosomes (5q21.1, 2p15, 8q21.11, 10q26.3 and
“This is the largest study to date, and the first to discover
the unique risk factors of Crohn’s disease in the Ashkenazi Jewish population,”
said Peter. “The prevalence of this disease is so much higher in Ashkenazi Jews,
and the involvement of genetic variants predominant in this population might
help understand why that is.”
The research team, funded by the New York
Crohn’s Disease foundation, also evaluated previous findings in non- Jewish
Europeans with Crohn’s disease and found that the genetic structure of the novel
regions associated with Crohn’s disease risk in the Ashkenazi Jewish group was
much less diverse than that of non-Jewish Europeans.
“Not only did we
discover different risk factors for Ashkenazi Jews, but we found that some
previously known risk factors are more potent to this population,” said Peter.
“Armed with this new information, we can begin to analyze the specific signals
to pinpoint causal genetic mutations, discover why they are malfunctioning, and
eventually develop novel treatment approaches.”
Since Dr. Crohn and his
colleagues first described this disease, Mount Sinai has remained at the
forefront of research and treatment for digestive diseases. Its specialists
today care for more patients with inflammatory bowel disease than any other
medical center in the US.
If medicines do not help, surgical bowel
resection may be needed to remove a damaged or diseased part of the intestine or
to drain an abscess.
The condition is marked by periods of improvement
followed by flare-ups of symptoms. Patients are at higher risk for small
bowel and colon cancer than those who do not have Crohn’s.
usually advised to eat a well-balanced, healthy diet, but certain types of foods
can make diarrhea and gas worse. Stress often makes the condition worse.
Medications are given to reduce symptoms, but there is no cure.
the gene discovery could eventually lead to early diagnosis, a better means of
treatment or maybe even a way to cure or prevent it.