Summary of VDR
The VDR gene provides instructions for making a protein called vitamin D receptor (VDR), which allows the body to respond appropriately to vitamin D. This vitamin can be acquired from foods in the diet or made in the body with help from sunlight. Vitamin D is involved in maintaining the proper balance of several minerals in the body, including calcium and phosphate, which are essential for the normal formation of bones and teeth. One of vitamin D's major roles is to control the absorption of calcium and phosphate from the intestines into the bloodstream. Vitamin D is also involved in several process unrelated to bone formation.
VDR attaches (binds) to the active form of vitamin D, known as calcitriol. This interaction allows VDR to partner with another protein called retinoid X receptor (RXR). The resulting complex of proteins then binds to particular regions of DNA, known as vitamin D response elements, and regulates the activity of vitamin D-responsive genes. By turning these genes on or off, VDR helps control calcium and phosphate absorption and other processes. Although the mechanism is not completely understood, VDR is also involved in hair growth. Studies suggest that this process does not require calcitriol binding.
The Benefits of The Vitamin D Receptor
In order to get the benefits of vitamin D3, it needs to work by eventually activating the VDR. Vitamin D has a potent anti-inflammatory role. It is particularly good for Th1 and Th17 dominant people. At the same time, it boosts the immune system in some ways. Vitamin D and a proper functioning VDR helps protects against:
- Osteoporosis (R)
- Cancer (R)
- Diabetes (R) “ Type 1 and 2 (R)
- Heart disease (R)
- Neurological diseases (R)
- Psoriasis (R)
- Infections (R)
- Multiple sclerosis (R)
- Asthma (R)
- Sun damage (R)
- Kidney inflammation and kidney disease death. (It should lower your creatinine levels.) (R)
- High Blood Pressure (Decreases Renin/angiotensin system). (R)
- Lupus/SLE (R)
- Arthritis (R)
- Scleroderma (R)
- Sarcoidosis (R)
- Sjogren's (R)
- Autoimmune thyroid disease (Hashimotos, Graves) (R)
- Ankylosing spondylitis (R)
- Reiter's syndrome (R)
- Uveitis (R)
The most popular benefits for vitamin D3 involve its role in bone health. Low blood levels of vitamin D3 are associated with lower bone density (R).
Clinical trials have shown that Calcitriol is helpful for people with lower bone density (R). VDR activation induces the expression of liver and intestinal phase I detox enzymes (e.g., CYP2C9 and 3A4) that play major roles in metabolizing drugs and toxins (R).
The Vitamin D Receptor is important for hair growth and loss of VDR is associated with hair loss in experimental animals (R). The VDR regulates the intestinal transport of calcium, Iron and other minerals (R).
Calcitriol/VDR increases dopamine by increasing the enzyme that limits the rate of step for dopamine production (tyrosine hydroxylase) (R). Calcitriol increases glial-derived neurotrophic factor (GDNF) (in vitro), which protects dopamine neurons.
Researchers hypothesize that inadequate levels of circulating vitamin D could lead to parkinsonian disorders (R). Active D has beneficial effects in cancer, especially breast, prostate and lung cancers (R).
It's better to have this gene increased most of the time.
Recommended name:Vitamin D3 receptor
Alternative name(s):1,25-dihydroxyvitamin D3 receptor
Nuclear receptor subfamily 1 group I member 1
- RS11574143 (VDR) ??
- RS1540339 (VDR) ??
- RS1544410 (VDR) ??
- RS2107301 (VDR) ??
- RS2228570 (VDR) ??
- RS2238136 (VDR) ??
- RS2239179 (VDR) ??
- RS2239182 (VDR) ??
- RS2239185 (VDR) ??
- RS2239186 (VDR) ??
- RS3782905 (VDR) ??
- RS3819545 (VDR) ??
- RS4516035 (VDR) ??
- RS7041 (VDR) ??
- RS731236 (VDR) ??
- RS757343 (VDR) ??
- RS7975232 (VDR) ??
To see your genotype, you should be logged in and have a file with your genotype uploaded.
Top Gene-Substance Interactions
VDR Interacts with These Diseases
- Seafood or Fish oil/DHA
Natural Ways to Increase Calcitrol and Vitamin D Receptor Gene Expression
- Exercise (R)- increases calcitriol, but not aerobic exercise (R).
- Parathyroid hormone (PTH) - increases Calcitriol/1,25 D3 (R),
- PTH-related peptide (R)
- Dopamine (R)
- Bile - specifically Lithocholic acid or LCA (R),
The VDR evolved from its ancient role as a detoxification nuclear receptor. LCA is produced from the gut bacteria (metabolizing liver-derived chenodeoxycholic acid). LCA travels to the colon, where the VDR binds to LCA or 1,25 D and activates the CYP3A4 and SULT2A genes facilitate disposal from the cell via the ABC efflux transporter (R).
- Omega-3:DHA, EPA (R), - Fish Oil/DHA
- Omega-6:Linolenic acid, Arachidonic acid (R),
- Curcumin (R)
curcumin is more active than LCA/Bile in driving VDR-mediatedtranscription and that it binds to VDR with approximately the same affinity as LCA,
- Resveratrol (R) - Potentiates VDR by: (1) potentiating 1,25D binding to VDR; (2) activating RXR; (3) stimulating SIRT1.
- Forskolin (R), - increases 1,25D3 from 25D3 in-vitro.
- Gamma Tocotrienol (R) - Tocopherols
- Vitamin E/alpha-tocopherol (R)- doesn't compete with calcitriol for the VDR.
- Dexamethasone (R) - doesn't compete with 1,25
- Interferon gamma -IFN-³ treatment inhibited 1,25D3 induction of 24-hydroxylase, the enzyme that breaks down 1,25 D3. This means 1,25D3 increased. (Technical: IFNy did not change the base level activity of the promoter, or change 1,25D binding to the VDR or nuclear VDR levels. IFN-³ impairs VDR-RXR binding to VDRE through a Stat1-mediated mechanism) (R),
- Estradiol - increases VDR expression (R, R2),
- Phytoestrogens (R),
- Testosterone (R),
- Prostaglandins (R),
- Bisphosphonates (R),
Curcumin and bile have a similar binding ability to the VDR and similar levels of gene expression (R). Curcumin, Bile, DHA, EPA, Arachidonic acid all compete with 1,25 D3 for binding.
Dexamethasone and alpha-tocopherol don't compete (R). A natural question to pose would be that if these are competitive binders and if they have lower binding capacity for the VDR, are they of use? The answer seems to be yes. High concentrations of PUFAs could occur in select cells or tissues and exert bioactivity (R).
Excess Bile/LCA given to rats caused the same effect that 1,25D3 would cause (in particular calcium transport activation) (R).
Kidney glandular might contain some 1,25 vitamin D.
What Inhibits The Vitamin D Receptor (VDR) or Calcitriol
- Caffeine decreases VDR production (R),
- Cortisol/Glucocorticoids decreases VDR production (R),
- Thyroid hormones repress VDR activation (R),
- TGF-beta reduces the activation of VDR/RXR combination, which results in VDR-mediated gene expression (R).
- TNF (R) (inhibits osteocalcin interaction with VDR, but not osteopontin)
- Corticosteroids decrease calcitriol (R),
- Phosphatonin, Ketoconazole, Heparin, and Thiazides decrease calcitriol (R).
Pathogens That Inhibit The Vitamin D Receptor
Many pathogens inhibit some aspect of the vitamin D system “ either the VDR, the ability of molecules to bind to it or the ability of VDR to cause gene expression. These are some examples, but I'm sure I haven't covered all of them known to the body of science.
- P. aeruginosin (often hospital acquired). Produces Sulfolipid ligand capnine.(R) Antibiotics don't work well (R).
- H. pylori (responsible for stomach ulcers). 50% of the global population has this. Produces Sulfolipid ligand capnine.(R)
Lyme/Borrelia “ Live Borrelia reduces VDR by 50 times (in monocytes) and dead Borrelia reduces it by 8 times (R) “ This could explain why people develop autoimmune conditions after Lyme infection.
Tuberculosis “ Reduces VDR 3.3-fold. (R)
Gliding biofilm bacteria have been shown to create Capnine “ Capnine (Cytophaga, Capnocytophaga, Sporocytophaga, and Flexibacter)
Shigella “ bacteria in stool and causes intestinal problems and diarrhea. It increases Caspase-3, which is a protein that breaks apart the VDR structure and thus limits the ability of VDR to perform gene transcription. (R)
- Ubiquitin (R) “ autophagy stops this
- Mycobacterium leprase “ produces mir-21 to target multiple genes associated with the VDR. (R)
- Epstein-Barr virus (EBV) “ Decreases VDR by a factor of about five (R) EBV also blocks the ability of VDR to produce products. (R)
- HIV “ binds to the VDR (R) and inhibits conversion to active D (R)
- Aspergillus fumigatus “ In cystic fibrosis patients, the fungus A. fumigatus has been shown to secrete gliotoxin, a toxin which dose-dependently decreases VDR.
- Cytomegalovirus “ CMV decreases VDR 2.2 fold. (R)
- Hepatitis C virus “ Inhibits CYP24A1, the enzyme responsible for breaking down excess 1,25-D. (R)
When bacterial products block the VDR, less of the CYP24A1 is produced, which results in excess active vitamin D “ as is the case in many autoimmune conditions.
Substances That Increase VDR
Substances That Decrease VDR
Vitamin D3 needs to convert to Calcitriol, the active form. Then, Calcitriol needs to attach to a specific receptor “ the Vitamin D Receptor or VDR.
Some infections of toxins black these receptors. If this happens, you wont get the health effects of Calcitriol or vitamin D3. After Calcitriol binds to the VDR, for many bodily functions, this complex then needs to go to the nucleus and bind with another protein such as RXR.
After that, there are cell-specific responses to regulate select genes that encode proteins that function in mediating the effects of vitamin D (R). In some cases, various steps can be left out. For example, in skin cells, the Vitamin D Receptor can have effects without Calcitriol to increase hair growth (via Wnt). (R)
Vitamin Ds Anti-Inflammatory Role
Vitamin D mainly lowers the adaptive immune system.
- Inhibits B cell proliferation. (R)
- Inhibits immunoglobulin (Ig) secretion. (R)
- Inhibits T cell proliferation. (R)
- A shift from Th1 or Th2 Dominant?">Th1 to Th2. (R, R2)
- Inhibits Th17 Immune System">Th17. (R)
- Increases Tregs and IL-10. (R)
- Decreases inflammatory cytokines (IL-1, IL-6, IL-8, Th1 Immune System">IL-12, TNF, Th17 Immune System">IL-17, IL-21). (R)
- Decreases TGF-beta (R)
- Decreases expression of MHCII and co-stimulatory molecules, which inhibits Dendritic Cell differentiation and maturation. (R)
If a word is hyperlinked, it means I've written about these at length and you can read more about it. Vitamin D also boosts the immune system: Vitamin D mainly stimulates the innate immune system.
- Crucial for T-Cell activation. In this sense its an immune booster. (R)
- Increase CD8+ T Cells, which is important in controlling viral infections.
- Increases Natural Killer T Cells. (R) “ good for preventing an autoimmune disease, but bad for asthma.
- Increases NK cells. (R) ( are associated with)
- Releases Antimicrobials in response to an infection such as cathelicidin and beta-defensin 4. (R)
Other Benefits of the Vitamin D Receptor
The most popular benefits for vitamin D3 is its role in bone health. Low blood levels of vitamin D3 are associated with lower bone density (R). Clinical trials have shown that Calcitriol is helpful for people with lower bone density (R).
VDR activation induces the expression of liver and intestinal phase I detox enzymes (e.g., CYP2C9 and 3A4) that play major roles in metabolizing drugs and toxins (R). The Vitamin D Receptor is important for hair growth and loss of VDR is associated with hair loss in experimental animals (R). The VDR regulates intestinal transport of calcium, Iron and other minerals (R).
Since many infections block the Vitamin D Receptor, our body cant fight them off well. Researches are using a combination of Calcitriol (active D) and antibiotics with good effects in many conditions.
Its a good idea to gradually eliminate pathogens over several years to minimize immune reactions. (R) Calcitriol/VDR increases dopamine by increasing the enzyme thats the rate limiting step for dopamine production (tyrosine hydroxylase) (R).
Calcitriol/VDR increases tyrosine hydroxylase in the hypothalamus (R), adrenal glands (R), substantia nigra (R) and likely other areas. This means that it increases productions of dopamine, adrenaline and noradrenaline.
Although having more neurotransmitters is a good thing, Tyrosine hydroxylase also increases oxidative stress, so it doesnt provide a free lunch. (R) Calcitriol increases glial derived neurotrophic factor (GDNF) (in vitro), which protects dopamine neurons. (R)
Researchers hypothesize that inadequate levels of circulating vitamin D could lead to dysfunction in the substantia nigra, an area of the brain in which the characteristic dopaminergic degeneration occurs in parkinsonian disorders (R).
A high prevalence of vitamin D deficiency has been reported in Parkinsons patients and Parkinsons has been associated with decreased bone mineral density (R). Active D has different effects in cancer.
In prostate cancer cells, the production of testosterone and DHT increased (BAD). (R) High levels of the enzyme that breaks down active D is found in lung cancer (R) and breast cancer (R). This would suggest that increasing its levels are good for breast and lung cancer.
Conditions with Increased Gene Activity
|Condition||Change (log2fold)||Comparison||Species||Experimental variables||Experiment name|
Conditions with Decreased Gene Activity
|Condition||Change (log2fold)||Comparison||Species||Experimental variables||Experiment name|
The following transcription factors affect gene expression (R):
It is uncertain whether Met-1 or Met-4 is the initiator.
- Dna Binding
- Steroid Hormone Receptor Activity
- Zinc Ion Binding
- Calcitriol Receptor Activity
- Lithocholic Acid Receptor Activity
- Sequence-Specific Dna Binding
- Retinoid X Receptor Binding
- Calcitriol Binding
- Lithocholic Acid Binding
- Negative Regulation Of Transcription From Rna Polymerase Ii Promoter
- Cell Morphogenesis
- Skeletal System Development
- Transcription Initiation From Rna Polymerase Ii Promoter
- Calcium Ion Transport
- Cellular Calcium Ion Homeostasis
- Signal Transduction
- Negative Regulation Of Cell Proliferation
- Positive Regulation Of Gene Expression
- Negative Regulation Of Keratinocyte Proliferation
- Positive Regulation Of Vitamin D 24-Hydroxylase Activity
- Bile Acid Signaling Pathway
- Positive Regulation Of Keratinocyte Differentiation
- Negative Regulation Of Transcription, Dna-Templated
- Positive Regulation Of Transcription From Rna Polymerase Ii Promoter
- Intestinal Absorption
- Positive Regulation Of Apoptotic Process Involved In Mammary Gland Involution
- Regulation Of Calcidiol 1-Monooxygenase Activity
- Mammary Gland Branching Involved In Pregnancy
- Vitamin D Receptor Signaling Pathway