Journal article
The autoimmune risk gene ZMIZ1 is a vitamin D responsive marker of a molecular phenotype of multiple sclerosis
Journal of Autoimmunity, Vol.78, pp.57-69
2017
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.
Details
- Title
- The autoimmune risk gene ZMIZ1 is a vitamin D responsive marker of a molecular phenotype of multiple sclerosis
- Authors/Creators
- N.L. Fewings (Author/Creator) - Westmead Institute for Medical ResearchP.N. Gatt (Author/Creator) - Westmead Institute for Medical ResearchF.C. McKay (Author/Creator) - Westmead Institute for Medical ResearchG.P. Parnell (Author/Creator) - Westmead Institute for Medical ResearchS.D. Schibeci (Author/Creator) - Westmead Institute for Medical ResearchJ. Edwards (Author/Creator) - Westmead Institute for Medical ResearchM.A. Basuki (Author/Creator) - Westmead Institute for Medical ResearchA. Goldinger (Author/Creator) - The University of QueenslandM.J. Fabis-Pedrini (Author/Creator) - Murdoch UniversityA.G. Kermode (Author/Creator) - Murdoch UniversityC.P. Manrique (Author/Creator) - Genomics (United Kingdom)J.L. McCauley (Author/Creator) - Genomics (United Kingdom)D. Nickles (Author/Creator) - University of California, San FranciscoS.E. Baranzini (Author/Creator) - University of California, San FranciscoT. Burke (Author/Creator) - The University of SydneyS. Vucic (Author/Creator) - The University of SydneyG.J. Stewart (Author/Creator) - The University of SydneyD.R. Booth (Author/Creator) - The University of Sydney
- Publication Details
- Journal of Autoimmunity, Vol.78, pp.57-69
- Publisher
- Academic Press Inc
- Identifiers
- 991005544130107891
- Copyright
- © 2016 Published by Elsevier Ltd.
- Murdoch Affiliation
- Institute for Immunology and Infectious Diseases
- Language
- English
- Resource Type
- Journal article
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- Collaboration types
- Domestic collaboration
- International collaboration
- Citation topics
- 1 Clinical & Life Sciences
- 1.203 Neuromuscular Disorders
- 1.203.147 Multiple Sclerosis
- Web Of Science research areas
- Immunology
- ESI research areas
- Immunology