The discovery of new genetic mutations involved in inflammatory intestinal disorders could lead to a better understanding of these common conditions, two scientists told the annual conference of the European Society of Human Genetics today (Monday 2 June).
Dr. Alexandra Zhernakova, from the Utrecht University Medical Centre, Utrecht, the Netherlands, and Dr. Eleonora Festen, from the University of Groningen, Groningen, the Netherlands, both working in the group of Professor Cisca Wijmenga, said that they had found common origins for two inflammatory diseases of the bowel, and that understanding the genetic profiles of these diseases will lead to better diagnosis, prevention, and, in the longer term, treatment. The research provides further support for the theory that common genetic factors are involved in a range of auto-immune and inflammatory diseases
Dr. Zhernakova and colleagues set out to study genetic mutations involved in coeliac disease. Coeliac disease is characterised by inflammation of the intestines leading to diarrhoea and, in children, failure to thrive through malnutrition. It is caused by an immune reaction to gluten, a protein found in wheat, rye, and barley in people who are genetically susceptible. When the immune system encounters gluten in the body, it cross-reacts with the bowel tissue and causes an inflammatory reaction. In the long-term this leads to flattening of the lining of the small intestine, which in turn hampers the absorption of nutrients. Currently, the only effective treatment is a totally gluten-free diet. The disease affects about 1% of the population in developed countries.
Using a genome-wide search, the team, in collaboration with researches from Ireland and the UK, analysed genetic variants in 778 coeliac cases, and in 1,422 controls from the UK. In phase II of this study the extensive collection of more than 5,000 coeliac cases and controls from the UK Ireland and the Netherlands were followed up for the top 1000 variants detected in phase I. The researchers found genetic mutations in eight new areas, seven of which contained genes involved in controlling immune responses.
"Three of these areas are also involved in Type 1 diabetes", said Dr. Zhernakova, "and, most interestingly, one overlaps with another intestinal inflammatory condition, Crohn's disease. This seems to show that common genes for inflammatory disease such as coeliac disease are not specific to the disease. It appears that these shared genetic mutations point to common molecular pathways."
Dr. Festen's team analysed the genetic variants in the immune pathway in a three-step design in a group of 1,851 patients with inflammatory bowel disease (IBD) and 1,936 controls. The two most common manifestations of this condition are Crohn's disease and ulcerative colitis. Crohn's disease can be found throughout the digestive tract, but most commonly affects the lower part of the small intestine. It causes extensive inflammation leading to swelling of the bowel lining and the formation of scar tissue; this results in pain and weight loss. In developed countries the disease affects around 45 people in every 100,000.