Parkinson’s Disease, low vitamin D and Vit. D genetics – Jan 2023

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Vitamin D deficiency and genetic polymorphisms of Vitamin D-associated genes in Parkinson’s Disease

European Journal of Neuroscience preprint DOI: 10.22541/au.167407862.25881100/v1
Barnali Ray Basu1, Randrita Pal1, Supriyo Choudhury2, Hrishikesh Kumar2, Sanjit Dey3, and Nilansu Das1
1Surendranath College
2Institute of Neurosciences Kolkata
3University of Calcutta Faculty Council for Post-Graduate Studies in Science

Parkinson’s Disease (PD) and vitamin D share a unique link as Vitamin D deficiency (VDD) prevails in PD. Thus, an in-depth understanding of Vitamin D biology in PD might be crucial for therapeutic strategies emphasizing Vitamin D. Specifically, explicating the effect of VDD and genetic polymorphisms of vitamin D-associated genes in PD, like

• VDR (Vitamin D Receptor) or
• GC (Vitamin D Binding Protein),

may aid the process along with polymorphisms of Vitamin D metabolizing genes (e.g., CYP2R1, CYP27A1) in PD. Literature review of single nucleotide polymorphisms (SNPs) related to Vitamin D levels [GC (GC1- rs7041, GC2-rs4588), CYP2R1, CYP24A1, CYP27B1] and Vitamin D function [VDR (FokI - rs2228570, Apal - rs7976091, BsmI-rs1544410, TaqI-rs731236)] was conducted to explore their relationship with PD severity globally. Furthermore, the DisGeNET database was utilized to explore the gene-disease associations in PD, and STRING alongside Cytoscape was utilized to identify critical genes associated with PD. VDR-FokI polymorphism was reported to be significantly associated with PD in Hungarian, Chinese, and Japanese populations, whereas VDR-ApaI polymorphism was found to affect PD in the Iranian population.
However, VDR-TaqI and BsmI polymorphisms had no significant association with PD severity.
Conversely, GC1 polymorphisms reportedly affected Vitamin D levels without influencing the disease severity.
CYP2R1 (excluding rs1993116) was also reportedly linked to clinical manifestations of PD.
Genetic polymorphisms might cause VDD despite enough sunlight exposure and vitamin D-rich food intake, enhancing inflammation, and thereby influencing PD pathophysiology.
Knowledge of the polymorphisms associated with vitamin D appears promising for developing new therapeutic strategies against PD.
 Download the PDF from VitaminDWiki

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VitaminDWiki - Overview Parkinson's and Vitamin D contains

• Vitamin D associated with Parkinson’s Disease in 55 studies, more studies needed- March 2022
• Parkinson's category has 117 studies
• Parkinson’s Disease and Vitamin D – review of 52 studies – May 2022
• Parkinson patients: 60 % taking Vitamin D – Dec 2019
• Low Vitamin D increases Parkinson's by 3X– July 2010 "only" a 30 year test, need more study
• Parkinson's disease prevented by Vitamin D, but small doses do not treat it - Aug 2023
• 10 clinical trials for PD with vitamin D intervention as of June 2023
• Parkinson’s Disease Summer School – alternative therapies included 60-80 ng of Vitamin D – Sept 2019
• Associated with PD are: Meta-analyses (12 ), Cognition (24 studies), Multiple Sclerosis (18 studies), VIRUS (4 studies), Omega-3 (3 studies), Vitamin D Receptor (11 studies)
• Note by the Founder of VitaminDWiki: I have twice recommended lots of Vitamin D to treat PD. Both got much better, but one had his doctor him cut back to just 2,000 IU. All of his recovery got reversed. With lots of vitamin D he could sing and bike, but now he can barely talk or walk

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VitaminDWiki - 5 studies in both categories Parkinson's and Genetics

This list is automatically updated

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VitaminDWiki - 11 studies in both categories Parkinson's and Vitamin D Receptor

This list is automatically updated

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VitaminDWiki – CYP27B1 category contains

The CYP27B1 gene activates Vitamin D in the Kidney,    Skin,    Lungs,    Brain,   Eyes   Breasts   etc.
Poor CYP27B1 is assocated with COVID, Miscarriage,   Lupus,   Alz, Parkinson, MSA,   Rickets

CYtochrome P450 family 27 subfamily B member 1    = 25-Hydroxyvitamin D3 1-alpha-hydroxylase

• 63 items in CYP27B1 category
• 344 articles in the Genetics
• 530 articles in Vitamin D Receptor
• 178 articles in Vitamin D Binding Protein
• CYP27B1 and other genes are less activated in seniors
• CYP27B causes many health problems – March 2020
• Every Parkinson’s brain had a poor CYP27B1 gene

What can be done if have a poor CYP27B1

• Larger doses of Vitamin D
• More Bio-available: Gut-friendly form, Topical form, taken with fatty meal, taken with evening meal
• Additional sources: UV
• Increase Vitamin D metabolism: additional Magnesium, Omega-3
  • All cytochrome P450 enzymes require Mg++ as a cofactor
• Increase the amount of Vitamin D in the blood that gets to cells: increase activation of VDR
  • See: Reasons for low response to vitamin D

Vitamin D blood test misses CYP27B1 and other genes

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VitaminDWiki – Cancers might alter CYP24A1 gene

This list is automatically updated

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VitaminDWiki – Vitamin D Binding Protein category listing has 178 items and the following introduction

Vitamin D Binding Protein (GC) gene can decrease the bio-available Vitamin D that can get to cells,

• GC is not the only such gene - there are 3 others, all invisible to standard Vitamin D tests
• The bio-available calculation does not notice the effect of GC, CYP27B1, CYP24A1, and VDR
• The actual D getting to the cells is a function of measured D and all 4 genes
• There is >2X increase in 8+ health problems if have poor VDBP (GC)
• It appears that VDBP only blocks oral vitamin D,
  • but NOT Vitamin D from sun, UV, topical or inhaled (tissue activated)
  • A clue: - Vitamin D from UV is 2X better for MS than oral Vitamin D

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VitaminDWiki – Vitamin D Binding Protein has a list of health problems

Increased Risk	Health Problem
11 X	Preeclampsia
6.5X	T1D in SA Blacks
6 X	Food Allergy
5 X	PTSD
4 X, 5X	Kidney Cancer
4 X	Poor Response to Oral Vitamin D
3 X	Ear infection
2.8 X	MS
2.5 X	Severe Autism
2 X	Colorectal Cancer
2 X	Prostate Cancer -in those with dark skins
1.3 X	Infertility