May 25, 2001
By Mindy Hung
New York - Using different investigational methods, independent research teams from the United States and Europe have pinpointed a gene mutation associated with increased susceptibility to Crohn's disease.
Gilles Thomas, PUPH, from INSERM, the French Institute of Health and Medical Research in Paris, France, and Judy Cho, MD, from the University of Chicago in Illinois, each led teams that found abnormalities on chromosome 16 encoding NOD2 — a protein associated with the innate immune system — in members of families with a history of Crohn's disease. Investigators speculate that the mutation may disrupt proper immune response to gut microbes, thereby leading to development of the disease.
The findings, which will be published in the May 31 issue of Nature, were presented Monday at Digestive Disease Week 2001 in Atlanta, Georgia.
The French study used a positional cloning strategy, which tracked and compared the known DNA sequences from members of 235 families with a history of the disease, to isolate first the genetic marker and then the region of the chromosome associated with the disease.
American researchers looked at the DNA of 416 families using a transmission disequilibrium test and case control analysis, an association method that allows testing for linkage in the presence of disequilibrium between an autosomal marker and a disease.
Although both sets of researchers agree that treatment arising as a direct result of these studies is far in the future, Cho told reporters, "These findings allow us to think completely differently about these disorders."
Gabriel Nuñez, MD, a member of the American team, noted that the implication of the NOD2 abnormality could allow for the development of more specific therapies. However, investigators warn that environment, lifestyle, and diet remain major risk factors contributing to development of the disorder.
Crohn's disease, an inflammatory bowel disease, tears up the lining of the digestive tract, causing severe diarrhea, bleeding, fever, and malnutrition. It often strikes young adults, with 1 in 4 patients reporting family history of the condition.
Current treatment consists of diet restriction and medication that suppresses inflammation and immune response.
Mindy Hung is an associate editor with Medscape.