Association between multiple sclerosis risk-associated SNPs and relapse and disability - a prospective cohort study

作者：Lin Rui; Taylor Bruce V; Simpson Steve Jr; Charlesworth Jac; Ponsonby Anne Louise; Pittas Fotini; Dwyer Terry; van der Mei Ingrid^*

来源：Multiple Sclerosis, 2014, 20(3): 313-321.

DOI：10.1177/1352458513496882

• Genetic
• genotype-vitamin D interaction
• prospective cohort
• disability
• relapse
• multiple sclerosis

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.

• 出版日期2014-3