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WT1 IFN 25(OH)D paper_ANS_Revision 1_for open access.docx (35.64 MB)

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

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journal contribution
posted on 2023-05-18, 04:44 authored by Lin, R, Bruce TaylorBruce Taylor, Jac CharlesworthJac Charlesworth, Ingrid van der MeiIngrid van der Mei, Christopher BlizzardChristopher Blizzard, Niall Stewart, Ponsonby, A-L, Dwyer, T, Pittas, F, Steve Simpson JRSteve Simpson JR
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 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.


Publication title

Acta Neurologica Scandinavica










Menzies Institute for Medical Research


Blackwell Munksgaard

Place of publication

35 Norre Sogade, Po Box 2148, Copenhagen, Denmark, Dk-1016

Rights statement

Copyright 2014 Wiley-Blackwell

Repository Status

  • Open

Socio-economic Objectives

Clinical health not elsewhere classified

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