Genetics of inflammatory bowel disease: from bench to bedside?

Epidemiological data, particularly concordance rates in twin pairs and in m ultiply affected families, provide strong evidence that both genetic and en vironmental influences are important in the development of the chronic inte stinal inflammation characteristic of Crohn disease and ulcerative colitis. Furthermore, supplementary data now suggest that not only susceptibility, but also disease behavior and response to therapy may have a strong genetic influence. The model of disease susceptibility most pertinent to the infla mmatory bowel diseases is that Crohn disease and ulcerative colitis are rel ated polygenic disorders. Recently, this model has received strong support from the results of genome-wide scanning and candidate gene studies carried out, in European, North American and Australian populations. In spite of a il potential difficulties related to disease and ethnic heterogeneity, cons istent replication of linkage has been found with distinct regions on chrom osomes 16, 12, 6 (the major histocompatibility complex) and most recently c hromosome 14. Whereas the linkages on chromosome 16 and 14 appear strongest in Crohn disease, the chromosome 12 locus appears most pertinent to ulcera tive colitis, and the HLA region appears more pertinent in all forms of inf lammatory bowel disease. The current challenge is to narrow these regions o f linkage and identify the susceptibility genes within the regions. The tas k may be greatly benefited by the recent successful sequence data available from the human genome project. Compelling data have emerged to suggest gen etic markers that may allow prediction of disease severity, and efficacy an d tolerability of immuno-suppressants commonly used in inflammatory bowel d isease.