Genetic and environmental determinants of 25-hydroxyvitamin D levels in multiple sclerosis

Mult Scler. 2015 Oct;21(11):1414-22. doi: 10.1177/1352458514563590. Epub 2014 Dec 22.


Background: Evidence is accumulating supporting a beneficial effect of vitamin D in multiple sclerosis (MS). Genome-wide association studies (GWAS) have shown significant associations between 25-hydroxyvitamin D (25(OH)D) and single nucleotide polymorphisms (SNPs) in key genes in the vitamin D metabolism.

Objective: To examine the association between 25(OH)D and six GWAS SNPs and environmental factors in 1497 MS patients.

Methods: Blood samples and lifestyle questionnaires were collected between 2009 and 2012. Genotyping of GC-, CYP2R1- and NADSYN1-SNPs was performed by TaqMan allelic discrimination (Life Technologies).

Results: We found significant associations between 25(OH)D and SNPs in GC (rs7041, p = 0.01 and rs2282679, p = 0.03) and CYP2R1 (rs10741657, p =1.8 × 10(-4)). Season of blood sampling (p = 2.8 × 10(-31)), sex (p = 1.9 × 10(-5)), BMI (p = 2.3 × 10(-5)), vitamin supplements (p = 7.0 × 10(-22)), and fish intake (p = 0.02) also had significant effects on 25(OH)D.

Conclusion: In this cross-sectional study, we found significant effects of environmental factors and SNPs in GC and CYP2R1 on 25(OH)D in MS patients. Since 25(OH)D might have protective effects in MS, and vitamin D supply is a modifiable factor, it may be important to include this in the MS treatment regimen.

Keywords: 25-hydroxyvitamin D; Multiple sclerosis; environment; genetics; vitamin D.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Biological Specimen Banks
  • Cross-Sectional Studies
  • Denmark
  • Environment*
  • Female
  • Genome-Wide Association Study
  • Genotype*
  • Humans
  • Male
  • Middle Aged
  • Multiple Sclerosis* / blood
  • Multiple Sclerosis* / etiology
  • Multiple Sclerosis* / genetics
  • Polymorphism, Single Nucleotide
  • Vitamin D / analogs & derivatives*
  • Vitamin D / blood
  • Young Adult


  • Vitamin D
  • 25-hydroxyvitamin D