Grant: Operating Grant

Although there is a general agreement that inflammatory bowel diseases - Crohn's disease and ulcerative colitis - are caused by the interaction of damaged genes and hazardous environmental factors, identification of such etiological factors has been slow despite significant research efforts. We performed a detailed re-analysis of the scientific literature on inflammatory bowel disease and concluded that a third group of factors, so-called epigenetic factors, may be of major importance for the normal functioning of gut. The main role of epigenetic factors is to regulate gene activity, and this is achieved by either chemical changes in DNA or by interaction of DNA with particular proteins. Epigenetic mechanisms may provide a new framework for evaluating the existing clinical, epidemiological, and molecular findings of Crohn's disease and ulcerative colitis that the traditional genetic research program cannot. Such features include the presence of disease in only one of identical twins, male - female differences in disease susceptibility, fluctuating course of the disease, discontinous inflammation with normal areas of gut separating areas of inflammation, among numerous others. In this project we will perform a large scale epigenetic analysis of over 25,000 gene regulatory regions in 40 sets of Swedish monozygotic and dizygotic twins of whom only one is affected with Crohn's disease. We will apply the microarray technology that allows for performing thousands and thousands of measurements in one single experiment. This research may lead to a better understanding of the changes in the regulation of genes and genomes that occur in Crohn's disease. The study will complement the traditional DNA sequence and environmental studies, and may help in understanding why the same gene sequence in some individuals is predisposing to inflammatory bowel disease while in other cases it is not.