The autoimmune risk gene ZMIZ1 is a vitamin D responsive marker of a molecular phenotype of multiple sclerosis
Journal of Autoimmunity. online 4 January 2017, http://dx.doi.org/10.1016/j.jaut.2016.12.006
N.L. Fewingsa, 1, P.N. Gatta, 1, F.C. McKaya, 1, G.P. Parnella, 1, S.D. Schibecia, J. Edwardsa, M.A. Basukia, A. Goldingerb, M.J. Fabis-Pedrinic, d, A.G. Kermoded, C.P. Manriquee, J.L. McCauleye, D. Nicklesf, S.E. Baranzinif, T. Burkeg, S. Vucica, g, G.J. Stewarta, g, D.R. Boothg,
- Vitamin D has already cleared 100 percent of lesions from over 1,000 MS patients in Brazil
- 1000 IU per kg Vitamin D for autoimmune diseases – Coimbra Aug 2013
- Interview of Dr. Coimbra - Vitamin D protocol for Autoimmune diseases – 2016
The articles in both MS and Genetics are:
- Vitamin D genes increase MS relapses in children by 2X – May 2019
- CYP2R1 gene problem increases Multiple Sclerosis risk by 1.4X – Dec 2018
- Multiple Sclerosis more likely if poor vitamin D genes - 22nd study – Aug 2017
- Mendelian proof that low vitamin D (due to 3 genes) increase risk of MS by 20 percent – Nov 2016
- Autoimmune risk gene ZMIZ1 is associated with both MS and Vitamin D – Jan 2017
- Multiple Sclerosis relapse in children is twice as likely having a Vitamin D Gene score of 6 – Oct 2016
- Multiple Sclerosis and obesity share some gene problems (as well as low vitamin D) – June 2016
- Genes make Multiple Sclerosis 2X more likely unless get more vitamin D - Aug 2015
- Multiple Sclerosis is connected to Vitamin D by gene to gene interactions – Aug 2014
- Multiple Sclerosis, gene expression, and vitamin D: Venn diagrams – Aug 2014
- Epigenetics of Multiple Sclerosis – March 2014
- Increased risk of multiple sclerosis risk in African Americans due to genes – June 2013
- 98 pcnt of genes that Vitamin D activates to reduce MS are also activated by Interferon -May 2013
- Transgeneration vitamin D deficiency related to MS was found in mice – Aug 2012
- Epigenetics, vitamin D, and Multiple Sclerosis
- Learning about MS and vitamin D in offspring from mice – Sept 2011
- Vitamin D targets 4 MS genes – May 2011
- Unable to find a gene linking vitamin D and MS – March 2011
- MS and vitamin D may be related by HLA gene – March 2010
- MS due to low level of vitamin D may be due to a specific gene – July 2010
The articles in both Autoimmune and Genetics are:
- Human Leukocyte Antigen (HLA) gene problem is associated with Autism, Vitiligo, T1 Diabetes, Celiac, etc
- Food allergies are associated with Vitamin D thru genes, etc. – March 2018
- Autoimmune risk gene ZMIZ1 is associated with both MS and Vitamin D – Jan 2017
- Impact of vitamin D on immune function: lessons learned from genome-wide analysis – April 2014
- Vitamin D, Allergy, and genetics – June 2012
Autoimmune Diseases have been increasing - Oct 2015
Highlights
- ZMIZ1, a pan-autoimmune disease risk gene, is downregulated in autoimmunity.
- Expression is tightly correlated with a gene module likely defining an immune state.
- The gene is predominantly expressed in monocytes and plasmacytoid dendritic cells.
- ZMIZ1 expression is affected by Vitamin D, Epstein–Barr virus infection, and therapy.
- ZMIZ1 may maintain a non-inflammatory immune cell phenotype.
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.