Vitamin D and Genetic Susceptibility to Multiple Sclerosis

Abstract

Multiple sclerosis (MS) is an autoimmune disease affecting the central nervous system (CNS), resulting from the interaction among genetic, epigenetic, and environmental factors. Vitamin D is a secosteroid, and its circulating levels are influenced by environment and genetics. In the last decades, research data on the association between MS and vitamin D status led to hypothesize a possible role for hypovitaminosis D as a risk factor for MS. Some gene variants encoding proteins involved in vitamin D metabolism, transport, and function, which are responsible for vitamin D status alterations, have been related to MS susceptibility. This review explores the current literature on the influence of vitamin D-related genes in MS susceptibility, reporting all single-nucleotide polymorphisms (SNPs) investigated to date in 12 vitamin D pathway genes. Among all, the gene codifying vitamin D receptor (VDR) is the most studied. The association between VDR SNPs and MS risk has been reported by many Authors, with a few studies producing opposite results. Other vitamin D-related genes (including DHCR7/NADSYN1, CYP2R1, CYP27A1, CYP3A4, CYP27B1, CYP24A1, Megalin-DAB2-Cubilin, FGF-23, and Klotho) have been less investigated and achieved more conflicting evidence. Taken together, findings from the studies reviewed cannot clarify whether and to what extent vitamin D-related gene variants can influence MS risk.