The autoimmune risk gene ZMIZ1 is a vitamin D responsive marker of a molecular phenotype of multiple sclerosis

N. L. Fewings, P.N. Gatt, F.C. Mckay, G.P. Parnell, S.D. Schibeci, J. Edwards, M.A.I. Basuki, A. Goldinger, M.J. Fabis-Pedrini, A. G. Kermode, C. P. Manrique, J. L. McCauley, D. Nickles, S. E. Baranzini, T. Burke, S. Vucic, G. J. Stewart, D. R. Booth

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Abstract

Multiple Sclerosis (MS) is a neurological condition driven in part by immune cells from the peripheral circulation, the targets for current successful therapies. The autoimmune and MS risk gene ZMIZ1 is underexpressed in blood in people with MS. We show that, from three independent sets of transcriptomic data, expression of ZMIZ1 is tightly correlated with that of hundreds of other genes. Further we show expression is partially heritable (heritability 0.26), relatively stable over time, predominantly in plasmacytoid dendritic cells and non-classical monocytes, and that levels of ZMIZ1 protein expression are reduced in MS. ZMIZ1 gene expression is increased in response to calcipotriol (1,25 Vitamin D3) (p < 0.0003) and associated with Epstein Barr Virus (EBV) EBNA-1 antibody titre (p < 0.004). MS therapies fingolimod and dimethyl fumarate altered blood ZMIZ1 gene expression compared to untreated MS. The phenotype indicates susceptibility to MS, and may correspond with clinical response and represent a novel clinical target.

Original languageEnglish
Pages (from-to)57-69
Number of pages13
JournalJournal of Autoimmunity
Volume78
DOIs
Publication statusPublished - 1 Mar 2017

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    Fewings, N. L., Gatt, P. N., Mckay, F. C., Parnell, G. P., Schibeci, S. D., Edwards, J., Basuki, M. A. I., Goldinger, A., Fabis-Pedrini, M. J., Kermode, A. G., Manrique, C. P., McCauley, J. L., Nickles, D., Baranzini, S. E., Burke, T., Vucic, S., Stewart, G. J., & Booth, D. R. (2017). The autoimmune risk gene ZMIZ1 is a vitamin D responsive marker of a molecular phenotype of multiple sclerosis. Journal of Autoimmunity, 78, 57-69. https://doi.org/10.1016/j.jaut.2016.12.006