Genetics of inflammatory bowel disease -: The candidate gene approach:: Susceptibility versus disease heterogeneity

Ulcerative colitis and Crohn's disease are complex diseases of unknown etiology. Several genes are involved in the susceptibility. These genes are necessary to suffer from these diseases but not sufficient. Environmental factors trigger the inflammatory response. Evidence is accumulating that this response is abnormal in these patients. Therefore, the study of genes that are involved in the regulation of the inflammation may help to clarify the pathogenesis of the disease. The working hypothesis is that HLA and cytokine gene polymorphisms, of extreme importance in the regulation of inflammation, contribute to determining the heterogeneity of the disease and the prognosis. In this case, the candidate genes are those involved in the regulation of the immune response of the host. These studies may be of great importance in the tailoring of an appropriate treatment for particular subgroups of patients. A premise for the success of these studies is to use a solid classification, which should take into account the dynamic process and the natural evolution of the disease; to use a carefully selected and ethnically matched group of healthy controls, and to use the advanced molecular biological typing techniques. In the present article, this concept is explored by taking into account some of the recent findings obtained with the HLA and cytokine gene polymorphisms in inflammatory bowel diseases. The results support the concept that these gene polymorphisms are of greater importance in determining the severity of the disease than in determining the susceptibility to suffer from the disease. From this point of view, these studies are complementary and a necessary addition to studies using the whole genome approach in the effort to understand the genetics of these chronic multifactorial diseases.