Molecular mechanism underlying the impact of vitamin D on disease activity of MS
Annals of Clinical and Translational Neurology, Article first published online: 22 AUG 2014
Kassandra L. Munger 1,†,*, Karl Köchert 2,†, Kelly C. Simon 1, Ludwig Kappos 3, Chris H. Polman 4, Mark S. Freedman 5, Hans P. Hartung 6, David H. Miller 7, Xavier Montalbán 8, Gilles Edan9, Frederik Barkhof4, Dirk Pleimes2, Rupert Sandbrink2,6, Alberto Ascherio1 and Christoph Pohl2,10
Objective
Some previous studies suggest modest to strong effects of 25-hydroxyvitamin D (25(OH)D) on multiple sclerosis (MS) activity. The objective of this study was to explore the mechanistic rationale that may explain potential clinical effects of 25(OH)D.
Methods
This study measured serum 25(OH)D levels and global gene expression profiles over a course of up to 2 years in patients starting treatment with interferon beta-1b (IFNB-1b) after a clinically isolated syndrome. MS disease activity was assessed by the number of gadolinium-enhancing lesions present on repeated magnetic resonance imaging (MRIs).
Results
The number of gadolinium-enhancing lesions was highly significantly associated with 25(OH)D levels. Conducting various systems-level analyses on the molecular level, multiple lines of evidence indicated that 25(OH)D regulates expression dynamics of a large gene–gene interaction system which primarily regulates immune modulatory processes modulating MS activity. The vitamin D response element was significantly enriched in this system, indicating a direct regulation of this gene interaction network through the vitamin D receptor. With increasing 25(OH)D levels, resulting regulation of this system was associated with a decrease in MS activity. Within the complex network of genes that are regulated by 25(OH)D, well-described targets of IFNB-1b and a regulator of sphingosine-1-phosphate bioavailability were found. The 25(OH)D effects on MS activity were additively enhanced by IFNB-1b.
Interpretation
Here, we provide mechanistic evidence that an unbalanced 25(OH)D gene expression system may affect MS activity. Our findings support a potential benefit of monitoring and managing vitamin D levels (e.g., through supplementation) in early MS patients treated with IFN-beta-1b.
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See also VitaminDWiki
- Overview MS and vitamin D
- 98 pcnt of genes that Vitamin D activates to reduce MS are also activated by Interferon -May 2013
- 3X more vitamin D from the sun if take MS drug Interferon-β – July 2012
- Review of clinical trials for Multiple Sclerosis with Vitamin D intervention – 2013
- Vitamin D reduces multiple sclerosis relapses, but not with interferon treatment – June 2012
The articles in both of the categories MS and Genetics are:
- People with Multiple Sclerosis have blunted responses to Vitamin D supplementation - Jan 2024
- Get Multiple Sclerosis while younger if have a poor CYP24A1 vitamin D gene – May 2023
- 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 of the categories MS and Vitamin D Receptor are:
- Multiple Sclerosis and Vitamin D Receptor Activators
- Multiple Sclerosis: is strongly related to poor Vitamin D receptors – umbrella review Oct 2024
- Poor Vitamin D Receptor increases the risk of Multiple Sclerosis in people of European descent – Feb 2024
- Multiple Sclerosis 2X-3X more likely if poor Vitamin D Receptor – Meta-analysis Feb 2020
- Risk of Multiple Sclerosis varies with the Vitamin D Receptor – meta-analysis Dec 2019
- Multiple Sclerosis and Vitamin D Receptor super enhancers – March 2019
- Vitamin D genes increase MS relapses in children by 2X – May 2019
- Immunological effects of vitamin D and their relations to autoimmunity – March 2019
- Inflammation and immune responses to Vitamin D (perhaps need to measure active vitamin D) – July 2017
- Multiple Sclerosis more likely if poor vitamin D genes - 22nd study – Aug 2017
- Multiple sclerosis (relapsing-remitting) increases activation of Vitamin D Receptor by 6.6 X – March 2017
- Multiple Sclerosis is more likely if poor Vitamin D Receptor (4X Mexico, 3X Iran)– Feb 2017
- Multiple Sclerosis much more likely if poor Vitamin D Receptor – several studies
- Multiple Sclerosis and the Vitamin D Receptor – meta-analysis July 2014
The articles in both of the categories MS and Vitamin D Binding Protein:
- Multiple Sclerosis 2.8 X more likely if poor Vitamin D Binding Protein – May 2022
- Gene variants can reduce Vitamin D response by 1.7X (14,000 IU daily, Multiple Sclerosis) – Dec 2021
- Vitamin D genes increase MS relapses in children by 2X – May 2019
- Mendelian proof that low vitamin D (due to 3 genes) increase risk of MS by 20 percent – Nov 2016
- Genes make Multiple Sclerosis 2X more likely unless get more vitamin D - Aug 2015
- Multiple Sclerosis is associated with about 1.5 X more Vitamin D Binding Protein – Jan 2015
- Late-stage MS associated with protein in spinal cord which blocks vitamin D – Jan 2013