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Modulating effects of WT1 on interferon-β-vitamin D association in MS

Citation

Lin, R and Taylor, BV and Charlesworth, J and van der Mei, I and Blizzard, L and Stewart, N and Ponsonby, A-L and Dwyer, T and Pittas, F and Simpson JR, S, Modulating effects of WT1 on interferon-β-vitamin D association in MS, Acta Neurologica Scandinavica, 131, (4) pp. 231-239. ISSN 0001-6314 (2015) [Refereed Article]

Copyright Statement

Copyright 2014 Wiley-Blackwell

DOI: doi:10.1111/ane.12315

Abstract

Objective:To investigate whether those genes involved in the vitamin D pathway modulate the relationship between 25-hydroxyvitamin D (25(OH)D) and IFN-β, the relationship between IFN-β and sun in predicting 25(OH)D, and the interaction between IFN-β and 25(OH)D in modulating relapse risk in patients with MS.

Methods:Prospective cohort study of 169 participants with MS and genotype data followed 20022005. Gene-IFN-β and gene-IFN-β-sun interactions predicting 25(OH)D evaluated by multilevel mixed-effects linear regression. Gene-IFN-β interactions with 25(OH)D in modulating in relapse risk assessed using survival analysis.

Results:The cohort was 71.6% female and of mean age 47.8. Two-independent intronic genotyped SNPs (rs10767935 and rs5030244) in WT1 significantly modified the IFN-β-25(OH)D association after adjustment (Pinteraction = 0.001, 0.0002; Padj = 0.003, 0.006, respectively). There was a marked difference in the interaction between self-reported sun exposure and IFN-β in predicting 25(OH)D by level of rs10767935, although this did not reach statistical significance. No SNPs modified the interaction between IFN-β and 25(OH)D in predicting relapse.

Conclusions:We have demonstrated that two-independent SNPs (rs10767935 and rs5030244) in WT1 modified the IFN-β-25(OH)D association in patients with MS. Some evidence was shown for a difference in the sun-IFN-β-25(OH)D association by level of rs10767935. These findings indicate that WT1 variants may play a role in altering the effects of IFN-β on vitamin D in MS.

Item Details

Item Type:Refereed Article
Keywords:interferon-b, genetic, vitamin D, multiple sclerosis
Research Division:Medical and Health Sciences
Research Group:Neurosciences
Research Field:Central Nervous System
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:Charlesworth, J (Dr Jac Charlesworth)
Author:van der Mei, I (Associate Professor Ingrid van der Mei)
Author:Blizzard, L (Associate Professor Leigh Blizzard)
Author:Stewart, N (Dr Niall Stewart)
Author:Pittas, F (Dr Fotini Pittas)
Author:Simpson JR, S (Dr Steve Simpson JR)
ID Code:96155
Year Published:2015 (online first 2014)
Web of Science® Times Cited:8
Deposited By:Menzies Institute for Medical Research
Deposited On:2014-10-21
Last Modified:2017-11-02
Downloads:0

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