Review Article: The genetics of inflammatory bowel disease

Recent epidemiological, clinical and molecular studies have provided strong evidence that inherited predisposition is important in the pathogenesis of chronic inflammatory bowel diseases. The model most consistent with the ep idemiological data suggests that Crohn's disease and ulcerative colitis are related polygenic diseases, sharing some but not all susceptibility genes. Investigators throughout the world have applied the complementary techniqu es of genome-wide scanning and candidate gene analysis. Four areas of linka ge have been widely replicated on chromosomes 16 (IBD1), 12 (IBD2), 6 (IBD3 -the HLA region), and most recently on chromosome 14. Fine mapping of these regions is underway. Of the 'positional' candidate genes, most attention h as centred on the genes of the major histocompatibility complex. Genes with in this region may determine disease susceptibility, behaviour, complicatio ns and response to therapy. Hope continues that studies of inflammatory bow el disease genetics will provide fresh insight into disease pathogenesis an d soon deliver clinical applications.