title: Genetic and environmental determinants of 25-hydroxyvitamin D levels in multiple sclerosis.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Neurology, Rigshospitalet, Copenhagen University Hospital, Danish Multiple Sclerosis Center, Denmark juliehejgaard@hotmail.com.
authors.forename: Julie H
authors.initials: JH
authors.lastname: Laursen
authors.affiliation: Department of Neurology, Rigshospitalet, Copenhagen University Hospital, Danish Multiple Sclerosis Center, Denmark.
authors.forename: Helle Bach
authors.initials: HB
authors.lastname: Søndergaard
authors.affiliation: Centre of Bioinformatics, Faculty of Science, University of Copenhagen, Denmark.
authors.forename: Anders
authors.initials: A
authors.lastname: Albrechtsen
authors.affiliation: Department of Clinical Biochemistry, Rigshospitalet, Copenhagen University Hospital, Denmark.
authors.forename: Ruth
authors.initials: R
authors.lastname: Frikke-Schmidt
authors.affiliation: Rigshospitalet, Copenhagen University Hospital, Danish Multiple Sclerosis Treatment Register, Denmark/Clinical Institute, Department of Clinical Epidemiology, University of Aarhus, Denmark.
authors.forename: Nils
authors.initials: N
authors.lastname: Koch-Henriksen
authors.affiliation: Department of Neurology, Rigshospitalet, Copenhagen University Hospital, Danish Multiple Sclerosis Center, Denmark.
authors.forename: Per
authors.initials: P
authors.lastname: Soelberg Sørensen
authors.affiliation: Department of Neurology, Rigshospitalet, Copenhagen University Hospital, Danish Multiple Sclerosis Center, Denmark.
authors.forename: Finn
authors.initials: F
authors.lastname: Sellebjerg
authors.affiliation: Department of Neurology, Rigshospitalet, Copenhagen University Hospital, Danish Multiple Sclerosis Center, Denmark.
authors.forename: Annette
authors.initials: A
authors.lastname: Oturai
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018070:Biological Specimen Banks; D003430:Cross-Sectional Studies; D003718:Denmark; D004777:Environment; D005260:Female; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000097:blood / Q000209:etiology / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000097:blood; D055815:Young Adult
chemical_list: D014807:Vitamin D; C104450:25-hydroxyvitamin D
keywords: 25-hydroxyvitamin D; Multiple sclerosis; environment; genetics; vitamin D