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]
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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 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|
|Objective Group:||Clinical Health (Organs, Diseases and Abnormal Conditions)|
|Objective Field:||Nervous System and Disorders|
|UTAS Author:||Lin, R (Ms Lin)|
|UTAS Author:||Taylor, BV (Professor Bruce Taylor)|
|UTAS Author:||Simpson Jr, S (Dr Steve Simpson JR)|
|UTAS Author:||Charlesworth, J (Dr Jac Charlesworth)|
|UTAS Author:||Pittas, F (Dr Fotini Pittas)|
|UTAS Author:||van der Mei, I (Associate Professor Ingrid van der Mei)|
|Year Published:||2014 (online first 2013)|
|Funding Support:||National Health and Medical Research Council (435713)|
|Web of Science® Times Cited:||16|
|Deposited By:||Menzies Institute for Medical Research|
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