Faulty Gene Found in People With Crohn's Disease

May 21, 2001 -- For the first time, scientists have identified a faulty gene that triggers an abnormal reaction to bacteria invading the gut of some people with Crohn's disease. Crohn's is a potentially devastating disease that affects the digestive tract.

American and European scientists, working separately, announced the promising findings today at a meeting of digestive disease experts in Atlanta. Knowledge of the gene and how it works in some -- and fails to work in others -- could help doctors find better, more specific ways to treat the debilitating disease that affects 1 in every 1,000 people in Western countries.

The American group was led by Gabriel Nunez, MD, who is an associate professor of pathology at the University of Michigan Medical School in Ann Arbor; the European group was led by Prof. Gilles Thomas of Fondation Jean Dausset, CEPH, in Paris. The full reports of both research groups appear in the May 31 issue of Nature.

Both groups of researchers believe the gene, called Nod2, is supposed to act as a sort of guardian that protects the body against bacteria that invade the intestines. In at least some people with Crohn's disease, the gene appears to be damaged and does not respond properly to keep harmful bacteria at bay. Instead, the immune system is triggered to attack the lining of the intestines -- causing sores and ulcerations -- instead of the bacteria. Nunez and colleagues made their findings by testing samples of genetic material from affected people with a high rate of Crohn's disease in their families.

"We've known for a long time that there is some role for genes and also for bacteria in the gut. The function was the missing link connecting those two things. Now we know Nod2 regulates the bacteria. It makes a lot of sense," says Nunez.

Whether people with Crohn's disease who have no history of it in their family -- so-called sporadic cases -- also may have the same or similar faulty gene is not known, because only people with the familial type were studied.

The next step in the research will be to start looking for the faulty gene in large groups of people with sporadic cases.

Although scientists will now concentrate on testing people with Crohn's disease for the mutation to determine how common it is, the findings don't rule out the possibility that other genes are involved in causing the disease, Charles O. Elson, MD, chairman of the national scientific advisory committee of the Crohn's and Colitis Foundation of America, tells WebMD.

"There are many other [possible] genes -- about 12 others -- that are as yet unidentified," says Elson, chief of gastroenterology at the University of Alabama at Birmingham. "This is the first -- and like your first date, it's always memorable."

The findings may mean people with the faulty gene will require different treatment than Crohn's patients without it. Researchers will also be looking to innovative ways to restore the gene to its proper function.

For now, Elson says, the gene is "not something you would want to go out and get tested for right away."

Estimates are that at least 4% of people in the general population who don't have Crohn's may have the faulty gene, so until scientists know more about what it means for people with the disease, there is little point in being tested for it.