Scientists find strong genetic link to Crohn's disease

Apr 17 2007

An international team of scientists believe they have identified a number of genes that may indicate a pre-disposal to developing Crohn's disease and say their discovery confirms the suspicion that the inflammatory bowel ailment has a strong genetic link.

As a rule Crohn's disease is diagnosed in people between the ages of 20 and 30; the debilitating condition usually affects the small intestine and can cause abdominal pain, diarrhea, rectal bleeding, weight loss and arthritis.

The researchers trawled through the entire genome of approximately 1,000 Crohn's patients and 1,000 healthy controls and tested more than 300,000 genetic variations.

Their findings were then tested in two additional sets of patients and controls and lead researcher John Rioux PhD now at the Universite de Montreal, says previous studies had identified two genes involved in the disease but they have now identified eight or nine genes.

According to the researchers their findings demonstrate that genetics play a crucial role in the disease but environmental factors also are involved; smoking appears to increase the risk.

The researchers believe that being able to pinpoint the genes that predispose people to Crohn's disease could lead to new ways to treat the disease.

A genetic component to Crohn's disease was indicated from a previous study by co-senior author Dr. Mark Daly of the MGH Center for Human Genetics Research and the Broad Institute and Dr.Rioux, where they found it appeared to run in families and was more common in certain ethnic groups, especially people of central and eastern European Jewish descent.

Experts suspect a fault exists in the response to the microbes that live in the human digestive system which in some way causes the immune system to attack the lining of the digestive tract, making it decay and become inflamed.

Rioux says some of the genes identified as risk factors are involved in the body's ability to deal with microbes.

Crohn's disease is named after Dr. Burrill Crohn who discovered it in 1932; it can affect any area from the mouth to the anus but most often affects the lower part of the small intestine, known as the ileum and is also called ileitis or enteritis.

A large number of those with Crohn's disease will ultimately need surgery to relieve symptoms that do not respond to medications or to correct complications such as intestinal blockage, perforation, abscess and bleeding.

It is often hard to diagnose because symptoms are similar to other intestinal ailments such as irritable bowel syndrome and ulcerative colitis.

In the United States alone as many as 1 million people suffer from Crohn's disease and ulcerative colitis.

This latest study used data from the Human Genome Project, a map of all the human DNA that is available to anyone on the Internet.

Researchers are able to compare the DNA of patients to the map version to see where one person differs from another.

The study also involved co-senior author Dr. Steven Brant of Johns Hopkins University and researchers from MGH Gastroenterology; the Broad Institute; Cedars Sinai Medical Center, Los Angeles; University of Montreal; Mt. Sinai Hospital, Toronto; University of Pittsburgh; the Hospital for Sick Children, Toronto; the University of Chicago; the University of Pittsburgh and Yale University.

The study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases, through the Inflammatory Bowel Disease Genetic Consortium.

The research is published in the journal Nature Genetics.