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

N L Fewings¹, P N Gatt¹, F C McKay¹, G P Parnell¹, S D Schibeci¹, J Edwards¹, M A Basuki¹, A Goldinger², M J Fabis-Pedrini³, A G Kermode⁴, C P Manrique⁵, J L McCauley⁵, D Nickles⁶, S E Baranzini⁶, T Burke⁷, S Vucic⁸, G J Stewart⁸, D R Booth⁹

Affiliations

¹ Centre for Immunology and Allergy Research, Westmead Institute of Medical Research, University of Sydney, Sydney, New South Wales, Australia.
² University of Queensland, Diamantina Institute, Translational Research Institute, The Queensland Brain Institute, University of Queensland, Australia.
³ Western Australian Neuroscience Research Institute, University of Western Australia, Nedlands, Western Australia, Australia; Institute for Immunology and Infectious Diseases, Murdoch University, Murdoch, Western Australia, Australia.
⁴ Institute for Immunology and Infectious Diseases, Murdoch University, Murdoch, Western Australia, Australia.
⁵ John P. Hussman Institute for Human Genomics and the Dr. John T. Macdonald Foundation Department of Human Genetics, University of Miami, Miller School of Medicine, Miami, FL 33136, USA.
⁶ Department of Neurology, University of California San Francisco, USA.
⁷ Western Clinical School, University of Sydney, Westmead Hospital, Sydney, New South Wales, Australia.
⁸ Centre for Immunology and Allergy Research, Westmead Institute of Medical Research, University of Sydney, Sydney, New South Wales, Australia; Western Clinical School, University of Sydney, Westmead Hospital, Sydney, New South Wales, Australia.
⁹ Western Clinical School, University of Sydney, Westmead Hospital, Sydney, New South Wales, Australia. Electronic address: david.booth@sydney.edu.au.

PMID: 28063629
DOI: 10.1016/j.jaut.2016.12.006

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

N L Fewings et al. J Autoimmun. 2017 Mar.

. 2017 Mar:78:57-69.

doi: 10.1016/j.jaut.2016.12.006. Epub 2017 Jan 4.

Authors

Affiliations

¹ Centre for Immunology and Allergy Research, Westmead Institute of Medical Research, University of Sydney, Sydney, New South Wales, Australia.
² University of Queensland, Diamantina Institute, Translational Research Institute, The Queensland Brain Institute, University of Queensland, Australia.
³ Western Australian Neuroscience Research Institute, University of Western Australia, Nedlands, Western Australia, Australia; Institute for Immunology and Infectious Diseases, Murdoch University, Murdoch, Western Australia, Australia.
⁴ Institute for Immunology and Infectious Diseases, Murdoch University, Murdoch, Western Australia, Australia.
⁵ John P. Hussman Institute for Human Genomics and the Dr. John T. Macdonald Foundation Department of Human Genetics, University of Miami, Miller School of Medicine, Miami, FL 33136, USA.
⁶ Department of Neurology, University of California San Francisco, USA.
⁷ Western Clinical School, University of Sydney, Westmead Hospital, Sydney, New South Wales, Australia.
⁸ Centre for Immunology and Allergy Research, Westmead Institute of Medical Research, University of Sydney, Sydney, New South Wales, Australia; Western Clinical School, University of Sydney, Westmead Hospital, Sydney, New South Wales, Australia.
⁹ Western Clinical School, University of Sydney, Westmead Hospital, Sydney, New South Wales, Australia. Electronic address: david.booth@sydney.edu.au.

PMID: 28063629
DOI: 10.1016/j.jaut.2016.12.006

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.

Keywords: Autoimmunity; Biomarker; Gene expression; Genetics; Multiple sclerosis; ZMIZ1.

PubMed Disclaimer

Publication types

Actions
Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Substances

Actions
Actions
Actions
Actions

Grants and funding

R01 NS088155/NS/NINDS NIH HHS/United States

LinkOut - more resources

Full Text Sources
- ClinicalKey
- Elsevier Science
Other Literature Sources
- scite Smart Citations
Medical
- ClinicalTrials.gov
- MedlinePlus Health Information

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

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

Affiliations

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

Authors

Affiliations

Abstract

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources

Medical