University Of Chicago, Hopkins Narrow Search For Inflammatory Bowel Disease Genes: New Study Provides Evidence For Important Gene-Gene Interaction

June 23, 1998

The largest, most comprehensive genome-wide study of patients with inflammatory bowel disease (IBD)--including Crohn's disease and ulcerative colitis--has focused and narrowed the search for the genes that cause this common and debilitating illness, a team of researchers from the University of Chicago Medical Center, Johns Hopkins Medical Institutions, and the Marshfield Medical Research Foundation in Marshfield, Wisconsin, report in the June 23 issue of the Proceedings of the National Academy of Scientists.

After typing 377 genetic markers on DNA from 439 IBD patients and 198 close relatives--from 174 separate families--the researchers identified regions on chromosomes 1p, 3q and 4q, which appear to contain genes that trigger the onset of the disease.

They also confirmed the role of one previously localized gene named IBD1, near the center of chromosome 16, that appears to act in concert with the disease gene on chromosome 1.

"The prospect of finding the genes involved is exciting because we know so little about what causes IBD," said Judy Cho, M.D., a gastroenterolgist at the University of Chicago and lead author of the study. "This genetic approach is our best bet for unraveling the complicated set of events that initiates these disorders and developing more specific therapies to treat the disease and not just the symptoms."

Steven R. Brant, M.D., director of the IBD Genetics Laboratory at Johns Hopkins and senior author of the study, said "Identifying the location of IBD genes is an important step toward the goal of preventing Crohn's disease and ulcerative colitis from occurring in genetically susceptible individuals." Brant is also an assistant professor of medicine.

Inflammatory bowel disease includes Crohn's disease (CD) and ulcerative colitis (UC), chronic disorders that primarily affect the intestines, causing pain, severe diarrhea, intestinal bleeding, weight loss and fever. They afflict about 250 out of every 100,000 people, usually beginning in adolescents and young adults. Symptoms vary in severity and duration; some patients suffer frequent prolonged attacks and others have fewer recurrences.

There is no cure for IBD. Treatments focus on controlling the inflammation through powerful drugs such as corticosteroids. Some patients require long-term use of medications, and many patients need surgery to remove inflamed or damaged portions of the intestines. Additionally, there is a greater risk of developing colorectal cancer.

Although environmental factors clearly contribute, these is strong evidence from studies of twins and affected families that IBD, especially Crohn's disease, has a genetic basis. The patterns of inheritance, however, are extremely complex. Multiple genes play a role--some affecting CD, some UC and some both.

IBD is two-to-eight times more common in Ashkenazi Jews. This is the first genome-wide study to look at Ashkenazi Jews, who made up 37 percent of the families in this study.

The complex inheritance patterns were reflected by this study's results. The researchers looked at families with either CD or UC, or both. They found a strong link between a gene on chromosome 1 for all families, but most of the evidence for this association came from families who were not of Ashkenazi Jewish heritage.

The linkage on chromosome 3q involved all families. But the association between the region on chromosome 4 was stronger for families that have both CD and UC, especially for those of Ashkenazi Jewish heritage.

"Although we now have some great clues, we are years away from isolating the individual genes that contribute to this disease," said Cho. Each suspect region contains hundreds of genes. "Once we narrow the search we still have to find out how these genes interact with the environment and each other. But it's still a tremendous boost to move one big step further toward unraveling this baffling disease and starting to develop better treatments."

Other researchers who contributed to this study include Stephen Hanauer, Barbara Kirschner, Dan Nicolae, Carter Fields, Michael Pickles and Yifan Fu from Chicago; Theodore Bayless, Patrick Rohal, Leslee Gold, Li Qin, Jasdeep Mann, Ethylyn Wang Jabs and Michele LaBuda from Hopkins; and James Weber from Marshfield.

Support for the research was provided by the Crohn's and Colitis Foundation of America; the Gastrointestinal Research Foundation; the Logan Center for Gastrointestinal Research, Univ. of Chicago; the Myerhoff Inflammatory Bowel Disease Center, Hopkins; the Mazza Foundation; the Edison Foundation; Glaxo Institute for Digestive Health; and the National Institutes of Health.

University of Chicago Medical Center

Related Inflammatory Bowel Disease Articles from Brightsurf:

People with inflammatory bowel disease still die earlier despite increase in life
A study comparing life expectancy of people with inflammatory bowel disease (IBD) and without found that, while life expectancy increased for both groups, people with IBD generally died sooner.

Cell therapy designed to treat inflammatory bowel disease
The UPV/EHU's NanoBioCel research group has for many years been developing systems enabling cells to be used as drugs.

Team develops wearable sensor to help people with inflammatory bowel disease
University of Texas at Dallas researchers have designed a wearable device that monitors sweat for biomarkers that could signal flare-ups of inflammatory bowel disease (IBD).

Antibiotics associated with increased risk of inflammatory bowel disease
Antibiotics use, particularly antibiotics with greater spectrum of microbial coverage, may be associated with an increased risk of new-onset inflammatory bowel disease (IBD) and its subtypes ulcerative colitis and Crohn's disease.

Yes, inflammatory bowel disease and celiac disease are linked
A systematic review and meta-analysis that has determined there is a nine-fold increased risk of having IBD for patients with a previous diagnosis of celiac disease.

The effects of inflammatory bowel disease on pregnancy
Inflammatory bowel disease (IBD) -- including Crohn's disease and ulcerative colitis -- often affects women of childbearing age.

5 major advances in inflammatory bowel disease (IBD) treatment
Summary of five impactful studies to be presented at the Crohn's & Colitis Congress, a partnership of the Crohn's & Colitis Foundation and the American Gastroenterological Association (AGA).

Researchers identify a possible cause and treatment for inflammatory bowel disease
In a study published online in PNAS on Jan. 20, 2020, Prof.

Does inflammatory bowel disease carry certain risks during pregnancy?
Pregnant women with inflammatory bowel disease (IBD) are more likely to undergo delivery by Caesarean section and face certain risks during pregnancy, according to an analysis published in Alimentary Pharmacology & Therapeutics.

Inhibiting a protease could improve the treatment of inflammatory bowel disease
Scientists at the CNIC and CSIC have identified a function of a protease that could be the future target of drugs to treat inflammatory bowel disease.

Read More: Inflammatory Bowel Disease News and Inflammatory Bowel Disease Current Events is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to