Phenotype-determining genes in inflammatory bowel disease.

Inflammatory bowel disease (IBD) has traditionally been categorized as either ulcerative colitis or Crohn's disease on the basis of clinical, radiological and histological criteria. Within these diseases however, significant heterogeneity is observed, suggesting the existence of phenotypic subtypes, based on features such as location and behaviour of disease. Evidence for a possible genetic basis for these subgroups emerged in the 1990s from epidemiological studies in multiply affected families. Recent advances in our understanding of the relationship between genotype and phenotype in IBD now challenge traditional clinical classifications, promising a taxonomy of disease based on precise molecular, rather than ambiguous clinical definitions. While many of the genes remain unidentified, the emerging data suggest that IBD comprises a heterogeneous family of oligogenic inflammatory disorders in which the specific clinical manifestations of disease in any individual are determined by the interaction of genetic and environmental factors. These data have highlighted both the importance and difficulties of classifying patients into accurately defined clinical subgroups, and suggest that a genetic basis for the observed disease heterogeneity may account for the discrepant findings from earlier genetic studies. Despite the considerable insights offered to investigators these advances have yet to impact on the clinical management of patients.