Shining Genetic Light on Your Vitamin D Levels

Vitamin D is essential to many processes in the body. It isn’t actually a vitamin at all but a prohormone that is synthesized in the skin when exposed to UV radiation.

Genes play a big role in your body’s susceptibility to low vitamin D levels. Read on to learn how to check your 23andMe results for your vitamin D genes and find solutions tailored to your specific genetic variants.

Vitamin D: What does it do for you?

Low Vitamin D levels are linked to various chronic conditions, from mood disorders to cancer risk to immunity to bone density. In general, higher vitamin D levels correspond to a lower risk of getting a variety of chronic diseases.

People think of vitamin D regarding bone health because it regulates calcium uptake to keep bones strong. But there is a lot more to vitamin D and your health. It acts in your cells to regulate the production of hundreds of different enzymes, influencing wellness in a multitude of ways.

How do you produce vitamin D?

Vitamin D is produced in the skin from exposure to sunlight. It is produced via a reaction with UVB radiation and cholesterol in the skin.[ref]

The initial form of vitamin D formed in the skin (or taken as a supplement) is the inactive form (cholecalciferol). It must go through several steps to convert into the active form.

  • First, it can be converted in the liver into 25-hydroxy vitamin D  – 25(OH)D – with the help of an enzyme coded for by the CYP2R1 gene.
  • That 25(OH)D then needs to go through one more step to be the active form that your cells need. To convert the 25(OH)D  into the active form – 1,25(OH)2D3  or calcitriol,  cells use an enzyme that is encoded by the CYP27B1 gene.

Your body’s 25(OH)D levels depend on how much you take in from food and sunlight.

The 1,25(OH)2D3 (calcitriol) levels are more tightly regulated, and the active form is converted when and where it is needed within the cells.

What exactly does vitamin D do?

In a nutshell, vitamin D can cause cells to turn on genes, making certain proteins needed in a cell.

To get a little more specific…
Inside your cells, vitamin D binds to the vitamin D receptor  (VDR).  This then causes VDR to get together with a couple of other proteins (one is a vitamin A-related receptor) and bind to different spots on the nuclear DNA. This activates the transcription of certain genes. In fact, vitamin D controls the expression of about 3% of the human genome. So, yeah, it’s pretty important.

Additionally, vitamin D can act as a hormone within cells to immediately cause non-DNA-related actions to take place – such as opening ion channels or causing the secretion of insulin.

The term pleiotropy gets used a lot in research papers about vitamin D. Pleiotropy just means that one gene (or, in this case, one product of a gene, calcitriol) can cause more than one completely different action or trait to occur.  In other words, vitamin D does a lot of stuff in the body that is seemingly unrelated. For example, Vitamin D is essential for calcium regulation and strong bones — and vitamin D is also essential for immune response. It is also important in cancer prevention, hypertension, atrial fibrillation, blood clots, inflammatory bowel disease, and autoimmune disease. [ref]

For Vitamin D to be used in the nucleus of cells, it needs to be transported there by a binding protein coded for by the GC gene, and then it needs to bind to the vitamin D receptor, which is coded for by the VDR gene.

Does supplementing with vitamin D actually do anything?

While low levels of vitamin D have been associated with a higher risk of a bunch of chronic conditions, supplementing with vitamin D doesn’t always give impressive results in placebo-controlled studies. For example, a recent clinical trial found little benefit for postmenopausal women when looking at bone mineral density. On the other hand, the amount of vitamin D used in the trial may have been too small to get a result.[ref]

One reason that some of the research studies and clinical trials of vitamin D supplementation showed no positive results is that the doses used may have been too low.

A study came out a couple of years ago claiming there was a statistical error in the calculation for the recommended daily vitamin D intake.[ref] This error changed the supplemental doses needed by a factor of 10.  Instead of 600 IU, some people may need 6,000IU+ per day. Other recent studies have backed this up, showing also that a person’s weight plays a big role in the amount of vitamin D needed for sufficiency.

A recent meta-analysis combining data from 52 different trials found that vitamin D supplementation did not impact overall mortality rates, but it did decrease the risk of death from cancer.


Vitamin D Geneotype Report:

Genetics can play a role in vitamin D levels in several ways, which makes sense when looking at the different steps involved in converting it to the active form, which then acts on the vitamin D receptors in a cell.

Below are genetic variants that have been shown in multiple research studies to impact vitamin D levels.

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GC Gene:

The vitamin D binding protein is coded for by the GC gene, and variants in the gene affect the total serum levels of 25(OH)D. The frequency of the variants in the GC gene varies in different population groups, which is thought to be a big part of the difference in vitamin D levels among populations.

Check your genetic data for rs2282679 (23andMe v4, v5; AncestryDNA):

  • T/T: typical vitamin D levels[ref]
  • G/T: somewhat lower total serum vitamin D levels
  • G/G: lower serum vitamin D levels[ref][ref]

Members: Your genotype for rs2282679 is .

Check your genetic data for rs7041 (23andMe v.4, v.5; AncestryDNA):

  • C/C: typical Vitamin D levels[ref]
  • A/C: somewhat lower vitamin D levels[ref]
  • A/A: lower Vitamin D levels[ref][ref]

Members: Your genotype for rs7041 is .

Check your genetic data for rs12512631 (23andMe v4; AncestryDNA):

  • T/T: typical vitamin D
  • C/T: typical vitamin D
  • C/C: increased vitamin D (both 25 and 1,25) levels.[ref]

Members: Your genotype for rs12512631 is .

Check your genetic data for rs1155563 (23andMe v4, v5; AncestryDNA):

  • T/T: typical vitamin D
  • C/T: lower vitamin D
  • C/C: significantly lower vitamin D levels[ref][ref]

Members: Your genotype for rs1155563 is .

VDR Gene: vitamin D receptor

After vitamin D (from sunlight, food, or supplements) has gone through the conversion steps, the active form, calcitriol, can act on cells through the vitamin D receptor (VDR), which is a transcription factor that turns a gene on or off.  Vitamin D receptors control various functions, including the activity of the immune system, skin, pancreas, and bone tissue. There have been many studies on these VDR gene variants, with some studies showing conflicting results. Note that there are popular websites online with reports on the VDR gene that are basing their + or – information on just a few older studies.[ref]

Check your genetic data for rs731236 (23andMe v.4, v.5; AncestryDNA):

  • G/G: typical[ref]
  • A/G: one copy of VDR Taql
  • A/A: VDR TaqI variant[ref]

Members: Your genotype for rs731236 is .

Check your genetic data for rs1544410 (23andMe v4, v5; AncestryDNA):

  • C/C: typical bone mineral density[ref]
  • T/T: carrier of BsmI variant, possible increased risk of low bone mineral density[ref][ref]

Members: Your genotype for rs1544410 is .

Check your genetic data for rs2228570 (23andMe v4 only):

  • A/A: typical
  • A/G: typical vitamin D levels[ref]
  • G/G: carrier of FokI variants, possibly decreased vitamin D levels, pos. increased risk of fractures[ref][ref][ref] increased risk of tuberculosis[ref]

Members: Your genotype for rs2228570 is .

Check your genetic data for rs7975232 (23andMe v4, v5; AncestryDNA)

  • C/C: half the risk of dengue fever[ref]
  • A/C: typical risk of dengue fever
  • A/A: typical risk of dengue fever

Members: Your genotype for rs7975232 is .

Check your genetic data for rs10783219 ( AncestryDNA)

  • A/A: typical
  • A/T: lower vitamin D levels, even with supplementation
  • T/T: lower vitamin D levels, even with supplementation[ref]

Members: Your genotype for rs10783219 is .

CYP2R1 Gene:

CYP2R1 is the gene that codes for the enzyme that converts D3 into 25-hydroxyvitamin D (25(OH)D).

Check your genetic data for rs2060793 (23andMe v4, v5; AncestryDNA):

  • A/A: lower vitamin D levels[ref]
  • A/G: typical vitamin D levels
  • G/G: higher vitamin D levels

Members: Your genotype for rs2060793 is .

Check your genetic data for rs1562902 (23andMe v4, v5; AncestryDNA):

  • T/T: higher vitamin D levels[ref]
  • C/T: typical vitamin D
  • C/C: typical vitamin D levels

Members: Your genotype for rs1562902 is .


CYP27B1 Gene:

The second step in the conversion to the active form of vitamin D involves CYP27B1 as a catalyst for the conversion of 25(OH)D into 1,25(OH)D. This takes place mostly in the kidneys or immune system cells. A couple of rare mutations (listed below) of CYP27B1 do affect the conversion to the active form of vitamin D, and these mutations are linked to rickets, a disease caused by the lack of vitamin D in childhood.

Check your genetic data for rs28934607 (23andMe v4; AncestryDNA):

  • A/A: pathogenic for Vitamin D related rickets[ClinVar]
  • A/G: carrier of a pathogenic allele
  • G/G: typical

Members: Your genotype for rs28934607 is .

Check your genetic data for rs28934605 (23andMe v4; AncestryDNA):

  • T/T: pathogenic for Vitamin D related rickets[ClinVar]
  • C/T: carrier of a pathogenic allele
  • C/C: typical

Members: Your genotype for rs28934605 is .

Check your genetic data for rs28934604 (23andMe v4; AncestryDNA):

  • T/T: pathogenic for Vitamin D related rickets[ClinVar]
  • C/T: carrier of a pathogenic allele
  • C/C: typical

Members: Your genotype for rs28934604 is .


Lifehacks:

Circadian Rhythm, Melatonin, and preventing damage from sun exposure:

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Supplement stacks:

If you are concerned about osteoporosis (check your genes here), you should consider taking vitamin K together with vitamin D.

 


Related Articles and Genes:

Circadian Rhythms: Genes at the Core of Our Internal Clocks
Circadian rhythms are the natural biological rhythms that shape our biology. Our master ‘clock’ genes drive this. It turns out that we also have circadian cycles (peripheral clocks) in most organs, such as the liver, pancreas, and fat cells.

Melatonin: Key to Health and Longevity
More than just a sleep hormone, melatonin is at the heart of many health topics. Your genetic variants play a big role in the production of melatonin. Learn how your lifestyle and diet interact with your melatonin-related genes.

Leveraging your gut microbiome to change your gene expression
Learn how your gut microbiome influences the expression of your core circadian rhythm genes.

The Link Between Vitamin D, MS, and Your Genes
Is there a link between Vitamin D and multiple sclerosis (MS)? Many researchers are speculating on a connection. Learn more about the research and check your own 23andMe and AncestryDNA data.

 

 


About the Author:
Debbie Moon is the founder of Genetic Lifehacks. Fascinated by the connections between genes, diet, and health, her goal is to help you understand how to apply genetics to your diet and lifestyle decisions. Debbie has a BS in engineering and also an MSc in biological sciences from Clemson University. Debbie combines an engineering mindset with a biological systems approach to help you understand how genetic differences impact your optimal health.