Scientists have pinpointed a genetic abnormality in humans — one originally discovered in plants — that increases susceptibility to Crohn's disease, a chronic inflammation that shreds the lining of the digestive tract.
American and French researchers said having a mutation to the gene on chromosome 16 increases a person's chances of developing an inherited form of the disease by at least 25 percent. However, not every person with the mutation becomes ill, they said.
The American and French groups presented their studies on Monday at a scientific meeting in Atlanta. The complete data will appear in the May 31 issue of the journal Nature, which released the study early.
The Nod2 gene encodes a protein associated with the innate immune system. That's the body's primitive first line of defense that recognizes invading bacteria and helps to mount a general attack.
Most life forms have an innate immune system. This is the first time that the plant gene was identified in humans, too.
Crohn's disease afflicts more than 500,000 people in the United States, most of whom are under 30. About one in four patients has a family history of the disease, which has encouraged researchers to find a genetic origin. So far, about 15 percent of patients tested have the altered form of the gene.
How the mutation contributes to Crohn's disease is unclear. When the Nod2 gene is damaged, researchers said, the immune system probably overreacts and mistakenly attacks healthy intestinal cells, causing chronic inflammation.
Some researchers said they found the plant gene link "surprising."
"Life is more uniform than we think," said gasteroenterologist Charles Elson, a Crohn's disease expert at the University of Alabama-Birmingham. He did not participate in the studies.
"We knew that the gene helps plants resist bacterial infection," Elson said. "So it's a very ancient part of the immune system."
Crohn's disease causes severe diarrhea, bleeding, fever and malnutrition. It is closely related to ulcerative colitis, so physicians often group the two disorders as inflammatory bowel disease.
Researchers believe that immune cells in the gut overreact to the presence of bacteria. The resulting inflammation causes the intestinal lining to ulcerate and break down.
The U.S. study tested DNA supplied by 416 families with a history of Crohn's disease. The French study tested 235 families.
Both groups focused on chromosome 16. Previous studies showed it was a promising site for genes involved with recognizing invading microbes.
The researchers said the Nod2 gene is found in monocytes, primitive defense cells that engulf invading microbes. The gene encodes a protein that recognizes the presence of lipopolysaccharides, a component of the outer membrane of bacteria.
Damaged versions of the gene produced an altered version of the protein that was less effective in recognizing invading bacteria, they said.
Healthy copies of the Nod2 gene appear to protect against Crohn's disease, they said. Other, yet-to-be-identified genes probably are involved in the disease.
Eventually, the Nod2 discovery may contribute to a gene-replacement therapy. However, researchers said the studies will have little impact on current Crohn's disease treatments.
"If we can figure out how these genes interact with each other and the environment, we may determine which strains of intestinal bacteria interact with Nod2 to increase or decrease intestinal inflammation," said University of Chicago gastroenterologist Judy Cho, co-author of the U.S. study.
Physicians say Crohn's disease is becoming more common, probably as a result of changing lifestyles and diet.
There is no cure. It is managed by diet restrictions and medication to suppress the immune system and calm inflammation. In severe cases, damaged portions of the intestine are surgically removed.