title: Vitamin D metabolic pathway genes and risk of multiple sclerosis in Canadians.
abstract: BACKGROUND
  Multiple sclerosis (MS) is determined by interactions between genes and environment and the influence of vitamin D adequacy has been proposed. Previous studies have shown that serum 25-hydroxyvitamin D (25(OH)D) levels are genetically influenced. Polymorphisms in vitamin D pathway genes are candidates for association with MS susceptibility.
  
  
  METHODS
  MS patients (n=1364) and their unaffected first-degree relatives (n=1661) were ascertained through the Canadian Collaborative study. Seventy-one SNPs, across four genes [vitamin D receptor (VDR), 1-alpha-hydroxylase (CYP27B1) enzyme, vitamin D binding protein (DBP), 24-hydroxylase (CYP24)], were genotyped and tested for association with MS susceptibility using TDT in PLINK. Secondary analyses included stratification for HLA-DRB1*15 and parent of origin transmission effects.
  
  
  RESULTS
  We found no significant association of vitamin D pathway genes with MS susceptibility after correction for multiple comparisons. However, the VDR Fok1 variant (rs2228570), selected for previously positive associations with MS susceptibility and 25(OH)D levels in MS patients showed marginally distorted transmission in DRB15-negative patients (p=0.03). There was no evidence for differential maternal versus paternal allele transmission.
  
  
  CONCLUSIONS
  The findings fail to directly connect vitamin D metabolism genes to MS susceptibility, despite a large sample size and comprehensive gene coverage.
authors: Wellcome Trust Centre for Human Genetics and Department of Clinical Neurology, University of Oxford, Oxford, UK.
authors: Sarah-Michelle
authors: SM
authors: Orton
authors: Sreeram V
authors: SV
authors: Ramagopalan
authors: Andrea E
authors: AE
authors: Para
authors: Mathew R
authors: MR
authors: Lincoln
authors: Lahiru
authors: L
authors: Handunnetthi
authors: Michael J
authors: MJ
authors: Chao
authors: Julia
authors: J
authors: Morahan
authors: Katie M
authors: KM
authors: Morrison
authors: A Dessa
authors: AD
authors: Sadovnick
authors: George C
authors: GC
authors: Ebers
mesh_terms: D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000235:genetics; D002170:Canada / Q000453:epidemiology; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics*; D005838:Genotype; D059811:HLA-DRB1 Chains / Q000235:genetics; D006801:Humans; D008297:Male; D009103:Multiple Sclerosis / Q000453:epidemiology* / Q000235:genetics* / Q000378:metabolism; D011110:Polymorphism, Genetic / Q000235:genetics; D018167:Receptors, Calcitriol / Q000235:genetics; D018570:Risk Assessment / Q000379:methods; D013250:Steroid Hydroxylases / Q000235:genetics; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000235:genetics / Q000378:metabolism; D014808:Vitamin D Deficiency / Q000453:epidemiology* / Q000235:genetics* / Q000378:metabolism; D014809:Vitamin D-Binding Protein / Q000235:genetics; D065668:Vitamin D3 24-Hydroxylase
chemical_list: D059811:HLA-DRB1 Chains; C507799:HLA-DRB1*15 antigen; D018167:Receptors, Calcitriol; D014809:Vitamin D-Binding Protein; D014807:Vitamin D; C104450:25-hydroxyvitamin D; D013250:Steroid Hydroxylases; D065668:Vitamin D3 24-Hydroxylase; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase