Inflammatory Bowel Disease:'New genes, rare variants & moving towards clinical practice'

Crohn's disease and ulcerative colitis are chronic inflammatory diseases of the gut (Inflammatory Bowel Diseases or IBD). In addition to inflammation of the gastrointestinal tract, 25% of IBD patients also have complaints outside the gastrointestinal tract, called extraintestinal manifestations, for example in the liver (primary sclerosing cholangitis). The development of IBD is influenced by several factors; environmental factors (such as smoking, medication and diet) and genetic factors play a role. The current hypothesis is an overactive immune reaction in a genetically sensitive patient on the intestinal bacteria composition (microbiome) of the intestine.Research focussed on genetic risk factors is important to increase our knowledge of the development of IBD. In this thesis we have identified and confirmed a number of new genetic risk variants (UBE2L3, BCL3, HNF4-α and CDH1) for IBD. In addition, we have found rare variants with ulcerative colitis (MUC2 gene) and primary sclerosing cholangitis. Rare variants, also called low frequency variants, are variants that influence protein expression.Besides variants that influence the disease development there are also variants that influence disease behaviour. These variants are also called disease-modifying genes. It appears that Crohn's disease patients who develop stenosis carry significantly more often the WWOX gene compared to Crohn's disease patients with mild disease course.Although precision medicine (individual based treatment) is not yet feasible, the developments in the genetics of IBD are coming closer to immediate improvement of patient care