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

Fewings, N. L., Gatt, P. N., McKay, F. C., Parnell, G. P., Schibeci, S. D., Edwards, J., Basuki, M. A., 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. and 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. doi:10.1016/j.jaut.2016.12.006


Author Fewings, N. L.
Gatt, P. N.
McKay, F. C.
Parnell, G. P.
Schibeci, S. D.
Edwards, J.
Basuki, M. A.
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.
Title The autoimmune risk gene ZMIZ1 is a vitamin D responsive marker of a molecular phenotype of multiple sclerosis
Journal name Journal of Autoimmunity   Check publisher's open access policy
ISSN 1095-9157
0896-8411
Publication date 2017-01-04
Sub-type Article (original research)
DOI 10.1016/j.jaut.2016.12.006
Open Access Status Not yet assessed
Volume 78
Start page 57
End page 69
Total pages 13
Place of publication London, United Kingdom
Publisher Academic Press
Language eng
Subject 2723 Immunology and Allergy
2403 Immunology
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.
Keyword Autoimmunity
Biomarker
Gene expression
Genetics
Multiple sclerosis
ZMIZ1
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
Queensland Brain Institute Publications
UQ Diamantina Institute Publications
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