Complexities of Crohn's Disease Brought to Light

In what could be the largest study ever undertaken into the underlying genetics of common diseases, a team of scientists and clinicians have identified new genetic links that increase susceptibility to Crohn's disease, one of a group of diseases called inflammatory bowel disease (IBD) that causes inflammation, pain, and ulcers. The researchers hope that by understanding the underlying causes of the disease, they can identify targets for new drug therapies.

Previous studies have identified 11 genes and loci (regions of the genome typically including one or more genes) that increase susceptibility to Crohn's disease.
After analyzing DNA samples from almost 12,000 people, researchers identified 21 additional genes. "We now know of more than 30 genetic regions that affect susceptibility to Crohn's disease," said Dr Jeffrey Barrett, lead researcher from the Wellcome Trust Centre for Human Genetics at the University of Oxford. "These explain only about a fifth of the genetic risk, which implies that there may be hundreds of genes implicated in the disease; each increasing susceptibility by a small amount."

Scientists have long known that genes, along with environmental factors, play a role in increasing the risk of people developing many common problems such as asthma, high blood pressure, cancer, rheumatoid arthritis, and heart disease. Three of the individual genes linked to Crohn's have previously been shown to influence the risk of type 1 diabetes and asthma, which suggests a possible common genetic mechanism. However, one of the most promising links is thought to be the CCR6 gene, which scientists believe to be part of the signaling process that causes white blood cells in the intestines to become over-active, leading to inflammation. These same white blood cells are also present in inflamed joints, implying that CCR6 may play a role in rheumatoid arthritis as well.

But the most unexpected link was that of the ORMDL3 gene on chromosome 17. This gene was already known to be a genetic risk factor for childhood asthma, but until now, had not been linked to Crohn's disease. "It's too early for us to say how Crohn's disease and many of these other diseases, including asthma, are linked at a biological level," said Dr Miles Parkes, Consultant Gastroenterologist at Addenbrooke's Hospital and the University of Cambridge, who also worked on the study. "However, we are building up a picture of the biology underlying Crohn's disease, and the more we understand about the underlying biology of these diseases, the better equipped we will be to treat them."

It is estimated that as many as 500,000 Americans suffer from Crohn's disease. It may occur in people of all ages, but mainly affects adolescents and young adults between 15 and 35. The disease also runs in families. Your chances of getting it are higher if a close family member has it. Also, people of Eastern European Jewish family background may have a higher chance of getting Crohn's disease.

Common symptoms include severe diarrhea and pain in the abdomen, but weight loss, joint pain, fever, bleeding from the rectum and skin problems may also occur. Severe complications are also possible, including intestinal blockage and malnutrition. Medications such as Abbott Laboratories Humira, UCB's Cimzia, or Johnson and Johnson's Remicade can greatly reduce the symptoms of Crohn's disease, and some people even have long periods of remission when they are free of symptoms, but as many as 80 percent of those suffering from the disorder will require surgery at some point.