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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; Booth, D R.
Afiliação
  • Fewings NL; Centre for Immunology and Allergy Research, Westmead Institute of Medical Research, University of Sydney, Sydney, New South Wales, Australia.
  • Gatt PN; Centre for Immunology and Allergy Research, Westmead Institute of Medical Research, University of Sydney, Sydney, New South Wales, Australia.
  • McKay FC; Centre for Immunology and Allergy Research, Westmead Institute of Medical Research, University of Sydney, Sydney, New South Wales, Australia.
  • Parnell GP; Centre for Immunology and Allergy Research, Westmead Institute of Medical Research, University of Sydney, Sydney, New South Wales, Australia.
  • Schibeci SD; Centre for Immunology and Allergy Research, Westmead Institute of Medical Research, University of Sydney, Sydney, New South Wales, Australia.
  • Edwards J; Centre for Immunology and Allergy Research, Westmead Institute of Medical Research, University of Sydney, Sydney, New South Wales, Australia.
  • Basuki MA; Centre for Immunology and Allergy Research, Westmead Institute of Medical Research, University of Sydney, Sydney, New South Wales, Australia.
  • Goldinger A; University of Queensland, Diamantina Institute, Translational Research Institute, The Queensland Brain Institute, University of Queensland, Australia.
  • Fabis-Pedrini MJ; 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.
  • Kermode AG; Institute for Immunology and Infectious Diseases, Murdoch University, Murdoch, Western Australia, Australia.
  • Manrique CP; 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.
  • McCauley JL; 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.
  • Nickles D; Department of Neurology, University of California San Francisco, USA.
  • Baranzini SE; Department of Neurology, University of California San Francisco, USA.
  • Burke T; Western Clinical School, University of Sydney, Westmead Hospital, Sydney, New South Wales, Australia.
  • Vucic S; 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.
  • Stewart GJ; 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.
  • Booth DR; Western Clinical School, University of Sydney, Westmead Hospital, Sydney, New South Wales, Australia. Electronic address: david.booth@sydney.edu.au.
J Autoimmun ; 78: 57-69, 2017 03.
Article em En | MEDLINE | ID: mdl-28063629
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.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Fenótipo / Fatores de Transcrição / Vitamina D / Autoimunidade / Esclerose Múltipla Tipo de estudo: Etiology_studies / Observational_studies / Risk_factors_studies Limite: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Ano de publicação: 2017 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Fenótipo / Fatores de Transcrição / Vitamina D / Autoimunidade / Esclerose Múltipla Tipo de estudo: Etiology_studies / Observational_studies / Risk_factors_studies Limite: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Ano de publicação: 2017 Tipo de documento: Article