Genetics and pharmacogenetics of inflammatory bowel diseases

The main forms of inflammatory bowel diseases (IBD) are Crohn’s disease and ulcerative colitis. These are chronic diseases, with periods of progression and remission. They are mostly characterized by digestive symptoms such as diarrhea, abdominal pain and weight loss. They affect young individuals and their frequencies have increased for the last decades. The etiology of these pathologies is not well understood, however genetic and environmental factors are involved. The treatment of IBD aims to control the inflammation and to extend periods of clinical remission. Infliximab is an anti-TNF-alpha antibody, leading to a clear improvement of the symptomatology. However, about 30 % of the patients do not response to this treatment. Genetic factors are certainly involved in these inter-individual differences. The purpose of our work was to find: 1- genetic factors implicated in the response to Infliximab in Crohn’s disease and 2- genetic factors predisposing to IBD. First we could show that both genes LTA and TNF, which are closely related, are not associated with the answer to Infliximab in Crohn’s disease. However, different polymorphisms of the ADAM17 gene were associated with a response to the treatment in our Belgian cohort.Second, we could demonstrate an association between an insertion/deletion in the IRF5 gene and IBD. The insertion allele, predisposing to IBD, is expected to create a new binding site for the SP1 transcription factor.