Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

BACKGROUND: The modulating effects of the multiple sclerosis (MS) risk-associated single-nucleotide polymorphisms (SNPs) on MS clinical course are not well established. OBJECTIVES: 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.

Original publication




Journal article


Mult Scler

Publication Date





313 - 321


Genetic, disability, genotype-vitamin D interaction, multiple sclerosis, prospective cohort, relapse, Adult, Alleles, Disability Evaluation, Disease Progression, Female, Gene-Environment Interaction, Genotype, Humans, Male, Middle Aged, Multiple Sclerosis, Relapsing-Remitting, Polymorphism, Single Nucleotide, Prospective Studies, Recurrence, Risk, Vitamin D