title: Association between multiple sclerosis risk-associated SNPs and relapse and disability--a prospective cohort study.
abstract: BACKGROUND
  The modulating effects of the multiple sclerosis (MS) risk-associated single-nucleotide polymorphisms (SNPs) on MS clinical course are not well established.
  
  
  OBJECTIVE
  The objective of this paper is to investigate whether known MS risk-associated SNPs were associated with clinical course, and whether these SNPs modified the 25(OH)D-relapse association.
  
  
  METHODS
  Using a prospective cohort of 141 participants with relapsing-remitting MS and genotype data followed between 2002 and 2005, genotype-vitamin D interactions and the genetic predictors of relapse were assessed using survival analysis, and genetic predictors of 25(OH)D and disability progression were evaluated by multilevel mixed-effects linear regression.
  
  
  RESULTS
  While no SNP reached statistical significance after multiple testing, five SNPs were associated with relapse, with significant cumulative genotype risk effects and two demonstrated significant allele dose-response. Two SNPs altered the 25(OH)D-relapse association with significant allele dose-response. Five SNPs modified levels of 25(OH)D, with significant cumulative genotype 'risk' effect, and three demonstrated significant allele dose-response. We found no consistent evidence for an association between any SNPs and disability.
  
  
  CONCLUSIONS
  Our study provides evidence for an association between known MS risk-associated SNPs and relapse. Our findings indicate gene-environment interactions may be an important mechanism on MS clinical course, and provide support for the role of vitamin D in MS relapse.
authors.affiliation: Menzies Research Institute Tasmania, University of Tasmania, Australia.
authors.forename: Rui
authors.initials: R
authors.lastname: Lin
authors.forename: Bruce V
authors.initials: BV
authors.lastname: Taylor
authors.forename: Steve
authors.initials: S
authors.lastname: Simpson
authors.forename: Jac
authors.initials: J
authors.lastname: Charlesworth
authors.forename: Anne-Louise
authors.initials: AL
authors.lastname: Ponsonby
authors.forename: Fotini
authors.initials: F
authors.lastname: Pittas
authors.forename: Terry
authors.initials: T
authors.lastname: Dwyer
authors.forename: Ingrid
authors.initials: I
authors.lastname: van der Mei
mesh_terms: D000328:Adult; D000483:Alleles; D004185:Disability Evaluation; D018450:Disease Progression; D005260:Female; D059647:Gene-Environment Interaction; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D012008:Recurrence; D012306:Risk; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000235:genetics
chemical_list: D014807:Vitamin D; C104450:25-hydroxyvitamin D
keywords: Genetic; disability; genotype-vitamin D interaction; multiple sclerosis; prospective cohort; relapse