Multiple sclerosis (MS) is a major autoimmune disorder of the central nervous system (CNS) in which inflammation, demyelination, axonal loss, and destructive structural and neuronal atrophy occur in every form of the condition and at any phase of the process. MS develops in a genetically susceptible individual exposed to a triggering environmental factor, probably a microbial agent. The individual born with a genetic predisposition inherits a set of susceptibility genes located in many regions of diverse chromosomes (1p, 5p13, 6p21-23, 10), the most common being alleles of the haplotype HLA-DR2 (DR15), which is quite prevalent among people of Northern European ancestry, including North Americans, most Europeans, and a small part of Latin Americans.
Genes recently recognized within single nucleotide polymorphisms (SNP), i.e., IL2RA, IL7RA, and EV15, contribute to the non-HLA genetic risk. Heterogeneity is noted in Japanese HLA-DR2-positive individuals with MS resembling Western types whereas HLA-DR2-negative cohorts have a severe opticospinal variety.
Protective genes such HLA-DRB1*11 appear to confer resistance to MS in Maltese populations. Other protectors are CD58, DBC1, and HLA-B*4402. Many racial groups are apparently more resistant to MS, particularly Asians and Amerindians, but groups resulting from intermixing with Europeans, i.e., Latin American Mestizos and African-Americans, acquire an increasing risk.
Ineludible epigenetic and environmental factors act together with the genetic component to condition development of the disease. Ancestral and more recent human migrations account for the current geographic distribution of MS and the diversity of its forms.
The natural history of MS is as varied as its phenotypes. There may be a single initial event, the clinically isolated syndrome (CIS), or a course of relapses or progression. The ability to identify genetically predisposed individuals will no doubt lead to changes in therapy outcomes, prognosis, and in the natural history of the disease.