The vitamin D pathway and Multiple Sclerosis

  • Dr Kate Greenhill, Menzies Research Institute Tasmania, Australia
  • Dr Jim Stankovich, Menzies Research Institute Tasmania, Australia
  • A/Prof Bruce Taylor, Menzies Research Institute Tasmania, Australia
  • Dr Ingrid Van der Mei, Menzies Research Institute Tasmania, Australia
  • Dr Jac Charlesworth, Menzies Research Institute Tasmania

We hypothesise that SNPs that tag vitamin D associated genes are enriched in multiple sclerosis (MS) genome wide association studies (GWAS). Genetic factors contribute 25-45% of the overall risk of MS. HLADRB1 is accepted as the main MS susceptibility locus. The search for other major loci has proved elusive with GWAS data indicating that there are a number of genes of small effect contributing either independently, or in combination, to risk of MS. There is strong epidemiological evidence of an association between vitamin D insufficiency and MS risk. Of the genes associated with MS a number are also present in the vitamin D pathway including HLADRB1*15. There is evidence to support an association between MS and SNPs within or near vitamin D pathway genes VDR and CYP27B1. Gene set enrichment analysis was used to determine whether there was an over-representation of SNPs within or near genes in vitamin D related pathways using data from the ANZgene GWAS for MS. Preliminary results suggest that SNPs with strong association signals located within and around these genes are enriched in the ANZgene MS GWAS. Genes of particular relevance to the vitamin D autocrine and paracrine activity also appear to be enriched. This analysis will add to the current understanding of the vitamin D pathway and MS susceptibility. Identification of such disease mechanisms not only assists in understanding the pathogenesis of MS but may also to lead to targets of intervention in the prevention and treatment of this debilitating disease.