Non-HLA Genes and Multiple Sclerosis

Abstract

Multiple sclerosis (MS) is an autoimmune demyelinating disease of the central nervous system. Identification of genetic variants that pose risks to MS is of high interest since they contribute largely to disease pathogenesis. A rich body of literature associated these risks with variants of HLA genes located mostly on the short arm of chromosome 6 (6p21). These genetic variations may result in alteration in protein function and are associated, therefore, with disease phenotype and therapy outcome. Although the HLA region has been routinely known to have the strongest correlation with MS, other genes found within and outside HLA locus are considered risk factors for MS. The objective of this review is to shed light on the non-HLA genes implicated with multiple sclerosis. Due to the interplay between the polygenetic and environmental factors, along with their differential contribution and genetic heterogeneity among populations, it is extremely challenging to determine the contribution of the non-HLA genes to the outcome and onset of MS disease. We conclude that a better assemblage of genetic factors involved in MS can have a critical impact on the establishment of a genetic map of MS that allows proper investigation at the expression and functional levels.