Links between the inflammatory bowel diseases (IBD), Crohn’s disease and ulcerative colitis, and other inflammatory diseases are being uncovered by an HRC-funded research programme out of the University of Otago, Dunedin.
Dr Rebecca Roberts, a senior research fellow in the Department of Surgical Sciences and 2008 HRC Sir Charles Hercus Health Research Fellowship recipient, says both diseases have strong genetic and environmental components. Crohn's disease has a peak age of onset of about 25 years, while ulcerative colitis has a peak age closer to 30.
“At the moment there is no known cure for either. If you can't control these diseases with drugs, your ultimate end point will be surgical intervention.”
“They are regarded as chronic inflammatory diseases. We don't know the exact cause but it is now widely accepted that these diseases arise through an inappropriate interaction of gut microbes with the immune system in people who have a genetic predisposition to IBD. The nature of the genetic predisposition is still being teased out.”
That is where genetics researchers like Dr Roberts come in, delving into hundreds of genes that could contribute to disease susceptibility.
Since the development of genome-wide association technology, researchers have identified more than 80 risk genes for Crohn’s disease and over 40 for ulcerative colitis.
“When you add all the genes together they only explain 20 per cent of the estimated heritability of Crohn's disease,” says Dr Roberts.
“There is a lot we still don't know, and I think when we started on this journey we thought we would have a lot more of the answers than we do. What we have now is more questions than answers.”
Among those questions are links with other chronic inflammatory diseases, such as the genetic overlap between Crohn’s disease and an inflammatory arthritis of the spine termed ankylosing spondylitis
There are studies that suggest 5 and 10 per cent of people with Crohn’s disease go on to develop ankylosing spondylitis, and vice versa, and some of the risk genes are shared, something Dr Roberts says they are very interested in exploring.
“It could be that they are two ends of the same disease continuum. It’s possible both diseases start in the gut and your genetic make-up determines whether you go on to develop Crohn’s disease or ankylosing spondylitis.”
Dr Roberts says they are also looking at genetic variation that may help predict patient response to drugs used to manage these inflammatory diseases - an area of study called pharmacogenetics.
Prospective genotyping may enable drug treatments to be tailored to the individual patient thereby maximising efficacy and minimising adverse side-effects.
“In the case of inflammatory diseases a lot of the drugs that are used to control the symptoms are quite toxic,” says Dr Roberts.
“Around 25 per cent of IBD patients are unable to tolerate some of the commonly used drugs due to side effects. We are talking everything from pancreatitis to flu-like symptoms, to bone marrow toxicity and drug-induced hepatitis.”
They have found a number of genetic variants which appear to associate with side-effects or resistance to treatment. In time, if a link is proven, it may be possible to develop genetic tests which could enable patients at high risk of a side effect to be identified before starting treatment.
Dr Roberts and her colleagues, during the course of the programme, have published three Nature Genetics papers as part of international consortia, as well as a number of smaller papers with more local relevance.