Personal viewpoint Epigenetics of inflammatory bowel disease

Understanding the causes and molecular mechanisms of Crohn’s disease and ulcerative colitis, the two forms of idiopathic chronic inflammatory bowel disease (IBD), is a major challenge in gastroenterology research. Significant eVort has been invested in uncovering genetic and environmental factors which may increase the risk of IBD, but progress has been slow, and no IBD specific factors have been detected so far. In this article we suggest that in addition to mutant genes and a hazardous environment, epigenetic factors may be relevant in understanding the aetiopathogenesis of Crohn’s disease and ulcerative colitis. This hypothesis is based on a number of clinical and molecular findings in IBD studies such as: (i) the maternal eVect in transmission of IBD from aVected parent to oVspring; (ii) parental diVerences in the degree of genetic anticipation; (iii) discordance of monozygotic twins aVected by IBD; (iv) genetic association studies demonstrating evidence for aberrant regulation of expression of cytokine genes; (v) sex eVects in association with HLA alleles and haplotypes; and (vi) epigenetic aspects of IBD treatment. It is suggested that inherited and/or acquired epigenetic defects, or epimutations, may be of aetiological and pathogenic importance in IBD. Epigenetic studies of Crohn’s disease and ulcerative colitis may have a significant impact on the field of IBD research.