Association between vitamin D receptor polymorphisms and multiple sclerosis: systematic review and meta-analysis of case–control studies
Cellular & Molecular Immunology , (7 July 2014) | doi:10.1038/cmi.2014.47
Kalthoum Tizaoui, Wajih Kaabachi, Agnès Hamzaoui and Kamel Hamzaoui
First portion of abstract – entire article can be rented from publisher for $4
Vitamin D receptor (VDR) polymorphisms have been studied as potential contributors to multiple sclerosis (MS). However, published studies differ with respect to study design and the significance of the effects detected. The aim of this study was to quantify the magnitude of the risk associated with the TaqI, BsmI, ApaI and FokI VDR polymorphisms in MS using a meta-analysis approach. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we conducted a systematic search and meta-analysis of the literature. Subgroup analyses were performed to detect potential sources of heterogeneity from the selected study characteristics. The stability of the summary risk was evaluated using sensitivity analyses. The meta-analysis included a total of 3300 cases and 3194 controls from 13 case–control studies.
There were no significant associations found between TaqI and BsmI polymorphisms and MS risk.
The association between the ApaI polymorphism and MS risk was significant in the homozygous and codominant models (P=0.013 and P=0.031, respectively), suggesting that the AA ApaI genotype might be a significant MS risk factor. Publication year and age significantly affected the association between TaqI polymorphisms and MS (P=0.014 and P=0.010, respectively), which indicates a protective effect of the major T allele. The AA ApaI and FF FokI genotypes are significant risk factors for MS. The association between the TaqI polymorphism and MS risk is significantly affected by study characteristics.
Current study was cited by 62 papers as of Nov 2019
- Vitamin D in Autoimmunity: Molecular Mechanisms and Therapeutic Potential Jan 2017 | https://doi.org/10.3389/fimmu.2016.00697 Free PDF
- Ultraviolet radiation, vitamin D and multiple sclerosis Oct 2015 https://doi.org/10.2217/nmt.15.33 Free PDF
- Predisposing role of vitamin D receptor (VDR) polymorphisms in the development of multiple sclerosis: A case-control study Aug 2016 https://doi.org/10.1016/j.jns.2016.05.053
See also Vitamin D Life
Pages listed in BOTH the categories VDR and MS
- 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 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
- Overview MS and vitamin D contains the following summary
Clinical interventions have shown that Vitamin D can prevent, treat, and even cure Multiple Sclerosis, at a tiny fraction of the cost of the drugs now used to treat it, and without side effects.
- Fact: Low Vitamin D results in higher risk of getting MS
Increase latitude leads to decreased Vitamin D, which leads to increased risk of MS
Dark skinned people are far more likely to get MS (dark skin people typically have low vitamin D)
Elderly (who typically have low vitamin D) are more likely to get MS
Is there increased risk in people who already have diseases associated with low vitamin D - TB, for example ? ? ?
Women typically have 3X increased MS risk then men (note: women typically have 20% lower levels of vitamin D than men)
Exception: women in very sunny climates and dark-skinned women have the same MS risk as men
Obese are 60% more likely to get MS
Multiple Sclerosis 42X more likely if light brown skin and smoke (both associated with low vitamin D) – July 2020
MS recurrence is much higher in spring - the lowest time of the year for vitamin D
increase in clouds/rainfall (which reduces available Vitamin D) is associated with increased risk of MS (Scotland, Western Washington)
MS incidence has increased 70% in a decade while the incidence of vitamin D deficiency doubled
Less MS in those with outdoor occupations PDF file, not a web page - Fact: MS uses up Vitamin D
- Fact: Lower vitamin D (due to MS using up Vitamin D while fighting the disease) results in many other health problems (such as broken bones), so depleted vitamin D levels must be restored.
- Fact: Vitamin D looks so promising for preventing and treating MS that there were 25 INTERVENTION clinical trials as of Feb 2014
- Fact: Vitamin D reduced the MS relapse rate far better than Fingolimod which is now used for that purpose.
- Note: Fingolimod costs $25,000/year while vitamin D, which works better and has no side effects is 1000 times less expensive.
- Fact: 98% of the genes affected by Interferon are also affected by Vitamin D
- Note: 1 week of Interferon = $4,700, 1 week of vitamin D 10,000X lower cost
- Fact: MS Doctors in Brazil recommending 40-100 ng/mL of Vitamin D
- Fact: Many MS forums are recommending vitamin D to treat MS, with some taking 5,000 to 10,000 IU daily
Observation: Risk of going from pre-MS to MS reduced 68 percent with 7100 IU vitamin D – RCT Dec 2012- This is an observation instead of a fact - it has not yet been confirmed.
- Fact: VERY LARGE doses of vitamin D have CURED 2,000 people of MS in Brazil
- Controversy: UVB fron sunlight or UVB bulb may be BETTER than Vitamin D for reducing the risk of getting MS
- Hypothesis: In addition to Vitamin D there are many other photoproducts produced by UVB that may promote health.
Summary: lack of consensus on how much to prevent, treat, or cure MS.
- How much Vitamin D to prevent many diseases - such as MS
- How much Vitamin D is needed to treat MS? There is currently no agreement
The recommendations range from 40 to 100 ng - which can result of a dose ranging from 3,000 to 20,000 IU/day - How Vitamin D is needed to Cure MS?: It appears that 20,000-140,000 IU daily may be needed to CURE the disease
You must be under the supervision of a doctor who knows what to watch for in your individual situation.
High doses of Vitamin D cannot be used as a monotherapy.
You will need to adjust the cofactors: Typically increasing Magnesium and Vitamin K2, and reducing Calcium intake.
Your doctor will monitor these and might increase your intake of Vitamins B2, C, as well as Omega-3899 - Epstein-Barr virus increases risk of Multiple Sclerosis by 32X - Jan 2022
- Multiple Sclerosis treated by Vitamin D, recommends investigating high dose Coimbra - Oct 2021
- Multiple Sclerosis patients had fewer COVID-19 problems (Note: many MSers take Vitamin D) – April 30, 2021
- Vitamin D Resistance hypothesis confirmed by Coimbra high-dose vitamin D protocol – April 2021
- Multiple Sclerosis relapses cut in half by 100,000 IU of Vitamin D every 2 weeks– RCT 2019