THE GENETICS OF INFLAMMATORY BOWEL DISEASE

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The purpose of these studies is to identify the genetic variants that are associated with inflammatory bowel disease (IBD). IBD is a chronic inflammation of the intestines and results in diarrhea, intestinal bleeding, and abdominal pain. It is comprised of two subtypes, Crohn s disease and ulcerative colitis. While medical therapies have improved over the past several years, medical therapies are only partially effective and a significant fraction of IBD patients require abdominal surgery. The identification of genetic variants that are associated with IBD may assist in the development of improved, more targeted therapies by delineating mechanisms of disease development. Such genetic studies have included tracking inheritance patterns in families with more than one member affected by IBD, as well as performing association studies where carriage of genetic variants are compared between unrelated individuals with and without IBD. Those genetic variants which are believed to play a direct role in disease susceptibility will then be further examined to define the functional effects of a particular variant in question. Of particular interest in IBD are genetic variation in the Nod2 (CARD15, caspase activation recruitment domain) gene. Studies in white blood cells from individuals carrying and not carrying the relevant mutations are performed. For Nod2 mutations, inflammatory responses to components of bacterial peptidoglycan (a component of their cell walls) are measured. Short term stimulation of Nod2 mutant white blood cells is associated with a reduced inflammatory response. Studies to examine chronic effects of bacterial stimulation characteristic of the intestine are ongoing.