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

Citation

Lin, R and Taylor, BV and Simpson Jr, S and Charlesworth, J and Ponsonby, A-L and Pittas, F and Dwyer, T and van der Mei, I, Association between multiple sclerosis risk-associated SNPs and relapse and disability - a prospective cohort study, Multiple Sclerosis, 20, (3) pp. 313-321. ISSN 1352-4585 (2014) [Refereed Article]

Copyright Statement

Copyright The Author(s) 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav

DOI: doi:10.1177/1352458513496882

Abstract

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

Objectives: 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.

Item Details

Item Type:Refereed Article
Keywords:genetic, genotype-vitamin D interaction, relapse, disability, multiple sclerosis, prospective cohort
Research Division:Medical and Health Sciences
Research Group:Public Health and Health Services
Research Field:Epidemiology
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Nervous System and Disorders
Author:Lin, R (Ms Lin)
Author:Taylor, BV (Professor Bruce Taylor)
Author:Simpson Jr, S (Dr Steve Simpson JR)
Author:Charlesworth, J (Dr Jac Charlesworth)
Author:Pittas, F (Dr Fotini Pittas)
Author:van der Mei, I (Associate Professor Ingrid van der Mei)
ID Code:85044
Year Published:2014 (online first 2013)
Funding Support:National Health and Medical Research Council (435713)
Web of Science® Times Cited:9
Deposited By:Menzies Institute for Medical Research
Deposited On:2013-06-12
Last Modified:2016-09-30
Downloads:0

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