VDR | SelfDecode | Genome Analysis

Summary of VDR

The VDR gene encodes the vitamin D receptor [R].

When vitamin D binds to and activates VDR, it helps maintain the balance of minerals like calcium and phosphate in the body. VDR controls the absorption of calcium and phosphate from the gut into the bloodstream. For this reason, VDR is important for the health of bones and teeth [R].

Vitamin D and VDR also support brain health by increasing dopamine production [R].

VDR furthermore contributes to hair growth, but the mechanism of this effect is unknown [R].

Vitamin D deficiency or a defective VDR pathway may contribute to:

Osteoporosis [R]
Cancer [R]
Diabetes [R, R]
Heart disease [R]
Neurological diseases [R]
Autoimmune diseases [R, R, R, R, R]
Infections [R]
Asthma [R]
Sun damage [R]
Kidney disease [R]
High Blood Pressure [R]
Arthritis [R]

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Protein names

Recommended name:

Vitamin D3 receptor

Short name:

VDR

Alternative name(s):

1,25-dihydroxyvitamin D3 receptor
Nuclear receptor subfamily 1 group I member 1

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Top Gene-Substance Interactions

VDR Interacts with These Diseases

Disease	Score

Fixes

FIXES:

Seafood or Fish oil/DHA
Curcumin
Bile

Fixes Advanced

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-mediated

transcription 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),

DHA, EPA, linoleic acid and arachidonic acid are all 10,000X less capable than 1,25 D3 at activating the VDR (R). Curcumin is 1,000X less capable than 1,25 D3 in inducing VDR gene expression (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)
Chlamydia (trachomatis)
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

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Substances	Interaction	Organism	Category

Substances That Decrease VDR

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Substances	Interaction	Organism	Category

Advanced Summary

VDR stands for the Vitamin D Receptor. We think of vitamin D3 as causing a bunch of health effects, but vitamin D3 is mainly just the beginning of the process that leads to its health benefits.

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 to Th2 . (R, R2)
Inhibits Th17 . (R)
Increases Tregs and IL-10 . (R)
Decreases inflammatory cytokines ( IL-1 , IL-6 , IL-8 , IL-12 , TNF , 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 breast cancer cells, estrogen (and aromatase) production decreased, while Testosterone/androgens increased (both GOOD). In adrenal cancer cells, it decreased DHT (GOOD).

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

Experimental Variables:

Condition	Change (log₂fold)	Comparison	Species	Experimental variables	Experiment name

Conditions with Decreased Gene Activity

Experimental Variables:

Condition	Change (log₂fold)	Comparison	Species	Experimental variables	Experiment name

Technical

The following transcription factors affect gene expression:

Gene Pathways:

Caution:

It is uncertain whether Met-1 or Met-4 is the initiator.

Molecular Function:

Biological Processes:

Drug Bank:

*synonyms

Synonyms/Aliases/Alternative Names of the Gene:

hypothetical protein| vdr| 1,25-dihydroxyvitamin D3 receptor| A306_01392| AS27_13398| AS28_12686| D623_10022134| GW7_07001| H920_11346| I79_021993| M959_12009| MDA_GLEAN10022508| N300_09530| N302_08686| N303_05509| N305_05899| N306_05139| N308_10170| N310_03014| N312_09244| N321_06707| N322_06580| N327_03991| N328_05472| N329_11597| N330_06188| N332_00538| N333_06636| N334_10682| N335_08764| N336_08501| N340_08921| Nr1i1| Nuclear receptor subfamily 1 group I member 1| PAL_GLEAN10010024| PANDA_009074| PPP1R163| protein phosphatase 1, regulatory subunit 163| TREES_T100021300| vdrbeta| Vitamin D3 receptor| vitamin D nuclear receptor variant 1| vitamin D receptor| vitamin D receptor beta| xVDR| Y1Q_021643| Y956_15947| Z169_15441

VDR (Vitamin D (1,25- dihydroxyvitamin D3) receptor)

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