title: Modulating effects of WT1 on interferon-β-vitamin D association in MS.
abstract: OBJECTIVE
  To investigate whether those genes involved in the vitamin D pathway modulate the relationship between 25-hydroxyvitamin D (25(OH)D) and IFN-β, the relationship between IFN-β and sun in predicting 25(OH)D, and the interaction between IFN-β and 25(OH)D in modulating relapse risk in patients with MS.
  
  
  METHODS
  Prospective cohort study of 169 participants with MS and genotype data followed 2002-2005. Gene-IFN-β and gene-IFN-β-sun interactions predicting 25(OH)D evaluated by multilevel mixed-effects linear regression. Gene-IFN-β interactions with 25(OH)D in modulating in relapse risk assessed using survival analysis.
  
  
  RESULTS
  The cohort was 71.6% female and of mean age 47.8. Two-independent intronic genotyped SNPs (rs10767935 and rs5030244) in WT1 significantly modified the IFN-β-25(OH)D association after adjustment (P(interaction) = 0.001, 0.0002; P(adj) = 0.003, 0.006, respectively). There was a marked difference in the interaction between self-reported sun exposure and IFN-β in predicting 25(OH)D by level of rs10767935, although this did not reach statistical significance. No SNPs modified the interaction between IFN-β and 25(OH)D in predicting relapse.
  
  
  CONCLUSIONS
  We have demonstrated that two-independent SNPs (rs10767935 and rs5030244) in WT1 modified the IFN-β-25(OH)D association in patients with MS. Some evidence was shown for a difference in the sun-IFN-β-25(OH)D association by level of rs10767935. These findings indicate that WT1 variants may play a role in altering the effects of IFN-β on vitamin D in MS.
authors.affiliation: Menzies Research Institute Tasmania, University of Tasmania, Hobart, Tas., Australia; Guangxi Center for Disease Prevention and Control, Nanning, China.
authors.forename: R
authors.initials: R
authors.lastname: Lin
authors.forename: B V
authors.initials: BV
authors.lastname: Taylor
authors.forename: J
authors.initials: J
authors.lastname: Charlesworth
authors.forename: I
authors.initials: I
authors.lastname: van der Mei
authors.forename: L
authors.initials: L
authors.lastname: Blizzard
authors.forename: N
authors.initials: N
authors.lastname: Stewart
authors.forename: A-L
authors.initials: AL
authors.lastname: Ponsonby
authors.forename: T
authors.initials: T
authors.lastname: Dwyer
authors.forename: F
authors.initials: F
authors.lastname: Pittas
authors.forename: S
authors.initials: S
authors.lastname: Simpson
mesh_terms: D000328:Adult; D000368:Aged; D015331:Cohort Studies; D005260:Female; D016162:Genes, Wilms Tumor; D005838:Genotype; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D016899:Interferon-beta / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000097:blood / Q000188:drug therapy* / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D012008:Recurrence; D013472:Sunlight; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000097:blood; D055815:Young Adult
chemical_list: D007155:Immunologic Factors; D014807:Vitamin D; D016899:Interferon-beta; C104450:25-hydroxyvitamin D
keywords: genetic; interferon-β; multiple sclerosis; vitamin D