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More than a century after its first clinical description and over 10 years after the introduction in clinical practice of treatments significantly altering its course, the cause of multiple sclerosis (MS) remains a puzzling mystery. MS etiology has a strong and complex genetic component. The hereditary tendency of this disease is indicated by both an increased relative risk in siblings compared with the general population, and an increased concordance rate in identical, compared with fraternal twins.1 Studies of half-siblings and adoptees2 also confirm that familial aggregation is significantly influenced by genetic factors. Epidemiologic studies characterizing the relationship between disease prevalence and both migration patterns and geographical gradients, in addition to high discordant rates observed in identical twins, also support, collectively, the important role of environmental influences. MS, therefore, similar to other complex diseases, originates from both genetic and environmental factors, but the way these latter interact to cause the disease is largely unknown.
The role of human leukocyte antigen (HLA) alleles within the major histocompatibility complex (MHC) on chromosome 6p21 in MS has been recognized for over 30 years.3 Genetic linkage and association studies have consistently …
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