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 2014 Wiley-Blackwell
Methods:Prospective cohort study of 169 participants with MS and genotype data followed 2002–2005. 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 Type:||Refereed Article|
|Keywords:||interferon-b, genetic, vitamin D, multiple sclerosis|
|Research Division:||Medical and Health Sciences|
|Research Field:||Central Nervous System|
|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 (Professor Leigh Blizzard)|
|Author:||Stewart, N (Dr Niall Stewart)|
|Author:||Pittas, F (Dr Fotini Pittas)|
|Author:||Simpson JR, S (Dr Steve Simpson JR)|
|Year Published:||2015 (online first 2014)|
|Web of Science® Times Cited:||8|
|Deposited By:||Menzies Institute for Medical Research|
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