Genomics and Proteomics

Inflammatory bowel disease (IBD) results from complex interactions between components in the intestinal lumen and multiple genes. 1 Linkage studies have led to the identification of NOD2 as a susceptibility gene. 2,3 Several other genomic loci have been implicated in IBD and may contain additional susceptibility genes. 4 These candidates represent probably only a small subset of all the genes involved in IBD pathogenesis. 1 Progress in understanding and treatment of IBD remains slow by this limited knowledge of genes and the gene products involved in disease, coupled with the complex and heterogeneous nature of the disease itself. 5 Until comprehensive insight into all cellular and extracellular players is complete, understanding of IBD will be imperfect. Conventional research focuses on different aspects of the disease that are thought to be important in the pathogenesis. Thus, T-cell functioning and regulation, the role of dendritic cells in mucosal immunity, innate immunity, and its specific receptors and gene hunting for disease susceptibility genes are to date important fields of basic IBD research. Significant discoveries in these specific fields, such as the identification of NOD2 as a disease susceptibility gene for Crohn's disease, unravel single features of the complex disease that IBD is. Moreover, only a small fraction of patients with Crohn's disease are homozygous for the mutated NOD2 alleles. Therefore, other genes must be involved in disease initiation and modulation. The NOD2 mutations seem to promote ileal localization, but colonic localization is also frequently noted in NOD2 homozygous patients. Although the identification of the NOD2 mutations has been a great breakthrough in IBD research, it also stresses the fact there is a long and narrow road ahead until the goal of clarifying IBD is reached.