Genetic and Environmental Factors Involved in the Pathogenesis of Multiple Sclerosis

Authors: L. Krížová 1;  B. Kollár 1;  Z. Čarnická 1;  P. Šiarnik 1;  D. Ježová 2;  P. Turčáni 1
Authors‘ workplace: I. neurologická klinika LF UK a UN Bratislava 1;  Ústav experimentálnej endokrinológie SAV Bratislava 2
Published in: Cesk Slov Neurol N 2013; 76/109(4): 430-437
Category: Review Article

Podporené grantom APVV-0028-10.


The analysis of human genome allowed identification of a great number of gene loci asso­ciated with an increased risk of multiple sclerosis. The most researched and clearly genetically associated with multiple sclerosis is the locus for a set of genes of the major histocompatibi­lity complex. The HLA-DRB1 allele is considered to be one of the most important risk alleles. Recently identified IL2RA, IL7RA, MGAT1, CYP27B1, CD6 and TYK2 are thought to be of potential causal relevance. Future genetic therapy for multiple sclerosis may involve induction of modified immunological mechanisms via modulated function of products of certain protective gene variants. Evidence is growing on a significant interaction between genetic, epigenetic and environmental factors. It has been suggested that several genes associated with multiple sclerosis are regulated by vitamin D. Moreover, gene variants causing significant changes in vitamin D levels have been identified. Mutation in the CYP27B1 gene may lead to a significant decrease in concentrations of the active form of vitamin D, resulting in an increased susceptibility to the disease. Future studies are expected to bring new information on causal alleles, regulatory mechanisms as well as epigenetic factors associated with multiple sclerosis.

Key words:
multiple sclerosis – risk genetic variants –risk locus – major histocompatibility complex – vitamin D


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