GENETIC SUSCEPTIBILITY TO MULTIPLE-SCLEROSIS

Twin studies have established that susceptibility to multiple sclerosis (MS) is partly genetic. Attempts to identify the relevant genetic loci have involved population-based studies, to detect associations between a genetic marker and MS, and family studies, to detect linkage between a putative marker and MS. Most of this genetic work is driven by the view that MS is an autoimmune disease. Thus, the focus has been mainly on genes known to be important in the immune response: human leukocyte antigen (HLA) genes, T-cell receptor genes, and immunoglobulin genes. To date, only the particular HLA-DR2 haplotype that is common in Caucasians can be concluded to be important in MS susceptibility in most populations. Studies of other genetic loci have been few, the data obtained often have been conflicting or controversial, and further studies are needed to clarify the biological significance of these loci in MS. Recommendations for further studies are provided in order to overcome some of the problems that have plagued earlier work in MS such as nonreproducibility of results.