Big Haul of Crohn's Genes Describes Disease Complexity

Scientists have linked 32 genetic variations to Crohn's disease, a bowel disorder, highlighting the difficulties facing researchers seeking treatments and the complexity of many common diseases. Crohn's disease affects between one in 500 and one in 1000 people in the industrialized world, causing inflammation, pain, ulcers and diarrhea. Scientists’ new research had tripled the number of genetic regions implicated in Crohn's, the most common form of inflammatory bowel disease, and many more were probably still undiscovered.

Jeffrey Barrett, a leader of the research from the Wellcome Trust Centre for Human Genetics at the University of Oxford, said the results explain only about a fifth of the genetic risk, which implies that there may be hundreds of genes implicated in the disease, each of them increasing susceptibility by a small amount.

Scientists have known for years that genes, along with environmental factors, play a role in increasing the risk that people will develop many common problems like high blood pressure, rheumatoid arthritis, asthma, cancer and heart disease. However, they are still trying to work out which parts of the 3 billion sub-units of DNA in our cells (genome) are actually responsible.

One way to find out is to conduct genome-wide association studies, in which genetic markers from thousands of volunteers are analyzed in order to identify genetic differences between healthy and diseased individuals.

The latest picture to emerge for Crohn's, which was reported in the journal Nature Genetics, represents the most complete picture yet assembled of the genetic influences on risk of a common disease. Significantly, three of the individual genes that have been implicated in Crohn's have previously been shown to influence risk of type 1 diabetes and asthma, suggesting a possible common genetic mechanism underlying these disorders. By pinpointing genes linked to the condition, researchers hope to find fresh targets for new drugs.

Modern biotech drugs like Abbott Laboratories's Humira, UCB's Cimzia and Johnson & Johnson's Remicade can help. However, many patients end up needing surgery.

One of the most promising is thought to be the CCR6 gene that believed to be part of the signaling machinery that causes white blood cells in the gut to become over-active, leading to inflammation. Barrett and colleagues said the same white blood cells are also present in inflamed joints, implying that CCR6 may play a role in rheumatoid arthritis as well, making it of added interest to the pharmaceutical industry.

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