Genetic background for immune-mediated diseases.

Gene variants (alleles) involved in the immune response are most likely selected during evolution. The allelic polymorphisms that may be advantageous in fighting harmful agents may be susceptibility genes in immune-mediated diseases. Identification of susceptibility genes is important because these genes encode proteins, which are most probably involved in the disease process. Hence, the identification of susceptibility genes may lead to an improved understanding of the pathogenesis and may therefore help the development of preventive and therapeutic measures. Susceptibility genes may be identified by analyzing genes known to be involved in immune responses (candidate gene search) or by analyzing gene markers evenly distributed over the genome (genome-wide scan). However, since several genes jointly contribute to disease susceptibility, the frequencies of single susceptibility genes may be quite high in the normal population. Moreover, different set of genes may predispose to the same clinical disease. It may therefore be very difficult to identify susceptibility genes, apart from the major histocompatibility complex (MHC) genes, which have now been shown to predispose to several immune-mediated diseases.