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

journal contribution
posted on 2023-05-17, 18:18 authored by Lin, R, Bruce TaylorBruce Taylor, Steve Simpson JRSteve Simpson JR, Jac CharlesworthJac Charlesworth, Ponsonby, A-L, Pittas, F, Dwyer, T, Ingrid van der MeiIngrid van der Mei

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.

Funding

National Health & Medical Research Council

History

Publication title

Multiple Sclerosis

Volume

20

Pagination

313-321

ISSN

1352-4585

Department/School

Menzies Institute for Medical Research

Publisher

Arnold

Place of publication

Hodder Headline Plc, 338 Euston Road, London, England, Nw1 3Bh

Rights statement

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

Repository Status

  • Restricted

Socio-economic Objectives

Clinical health not elsewhere classified

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