Genetic link between Crohn's and asthma discovered

Jul 2 2008

British scientists have discovered a link between the bowel disorder Crohn's disease and asthma.

Research into the genetic causes of Crohn's disease has revealed that the gene ORMDL3, known to be a risk factor for childhood asthma, is also associated with Crohn's disease, and in the process links between the condition and other diseases have been found.

The international collaboration of researchers have also uncovered a clutch of new Crohn's-related genes expanding the total now known from 11 to 33 - this was done by using DNA samples from almost 12,000 people from the UK, Europe and North America.

Crohn's is a complex auto-immune disease that affects up to one in 500 people - it is an inflammation of the gastrointestinal tract which causes pain, ulcers and diarrhoea. The disease can strike at any age, but onset is typically between 15 and 40 years old and most sufferers will need surgery at some point.

Evidence suggests the disorder is affected by large numbers of genes, and previous studies had already identified 11 genes and sections of DNA -loci- where one or more unknown genes may reside which increase susceptibility to the disease.

Consultant gastroenterologist Dr. Miles Parkes from Addenbrooke's Hospital Cambridge, says it is too early to say how Crohn's disease and many other such diseases, including asthma, are linked at a biological level but a picture of the biology underlying Crohn's disease is being built which will lead to a better understanding and better treatment.

Lead author of the study Dr. Jeffrey Barrett from the Wellcome Trust Centre for Human Genetics at the University of Oxford, says it is now known that more than 30 genetic regions affect the susceptibility to Crohn's disease, but these only explain about a fifth of the genetic risk.

Dr. Barrett says this implies that there may be hundreds of genes implicated in the disease, each increasing susceptibility by a small amount which highlights the complexity of diseases such as Crohn's.

Among the findings are loci containing genes known to be implicated in a number of other common diseases including diabetes, rheumatoid arthritis and psoriasis but the genetic relationship between Crohn's and these other diseases is not always simple.

The researchers say the work is about identifying targets for new drugs therapies and as Crohn's disease can be a very serious condition, the sooner the underlying causes are understood, the sooner new treatments will be devised to help patients.

One of the most likely candidates is the CCR6 gene, which is thought to be part of the signalling machinery that causes white blood cells in the gut, known as Th17 cells, to become over-active, leading to inflammation. These cells, are also present in inflamed joints, implying that CCR6 may also be relevant to rheumatoid arthritis.

Dr. Mark Walport, Director of the Wellcome Trust says research such as this highlights the important relationships between different diseases and, as such, may offer valuable insights into the pathways that lead to common symptoms such as inflammation.

The research is published in the journal Nature Genetics.