Shining Genetic Light on Your Vitamin D Levels

Vitamin D is essential to so many processes in the body! It isn’t actually a vitamin at all, but a prohormone that is synthesized in the skin using cholesterol in a chemical reaction with UVB radiation from the sun. Most people think of vitamin D in regards to bone health because it regulates the uptake of calcium in our intestines, but it also acts in the nucleus of cells to regulate the production of hundreds of different enzymes, influencing health in a multitude of ways.

Genes play a big role in your body’s vitamin D levels.  Read on to learn how to check your 23andMe results for your vitamin D genes.

Importance of Vitamin D

Vitamin D levels have been associated with a variety of 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.vitamin_D_levels_chart

While low levels of vitamin D have been associated with 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 that claimed there was a statistical error in the calculation for the recommended daily intake of vitamin D.[ref] This error changed the supplemental doses needed by a factor of 10; instead of 600IU, 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 that combined the 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.

Conversion of vitamin D: from skin production to the active form

Genes involved in converting vitamin D to the active form.

 

The form of vitamin D produced in our skin is the biologically inactive form, cholecalciferol or Vitamin D3. It is formed through a reaction between UVB rays from sunlight and cholesterol in our skin.

Vitamin D3, cholecalciferol,  must then be converted to the active form that our body uses.

The first step in the conversion takes place in the liver, where cholecalciferol is hydroxylated in the liver into calcidiol (25(OH)D) using an enzyme that is encoded by the gene CYP27A1.

Calcidiol (25(OH)D) can then be converted in the kidneys or macrophages into calcitriol, the biologically active form of vitamin D also known as 1,25(OH)2D.  This conversion takes place using an enzyme coded for by the gene CYP27B1.

For Vitamin D to be used in the nucleus of cells, it needs to be transported there by a binding protein that is 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.


Vitamin D Genetic Variants:

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.

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 vary in different population groups, and this 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: Normal vitamin D levels [ref]
  • G/T: Somewhat lower total serum vitamin D levels
  • G/G: Lower serum vitamin D levels[ref][ref]

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

  • C/C: Normal Vitamin D levels [ref]
  • A/C: Somewhat lower vitamin D levels[ref]
  • A/A: Lower Vitamin D levels [ref][ref]

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

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

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

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


VDR (vitamin D receptor) Gene:

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 a variety of different 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/A: VDR TaqI variant [ref]

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

  • C/C: Normal bone mineral density [ref]
  • A/A: Carrier of BsmI variant, possible increased risk of low bone mineral density[ref] [ref]

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

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

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

  • C/C: Half the risk of dengue fever [ref]
  • A/C: normal risk of dengue fever
  • A/A: normal risk of dengue fever

CYP2R1 Gene:
CYP2R1 is the gene that codes for the enzyme that converts cholecalciferol into calcifediol in the liver.

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

  • A/A: Lower vitamin D levels  [ref]
  • A/G: Normal vitamin D levels
  • G/G: Higher vitamin D levels

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


CYP27B1 Gene:

The second step in the conversion to the active form of vitamin D involves CYP27B1 as a catalyst for the conversion of calcifediol to calcitriol. While there are several common polymorphisms in CYP27B1 that have been studied in regards to vitamin D related conditions, none of them have been definitively shown to have an effect. 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: Normal

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: Normal

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: Normal

Lifehacks

Circadian Rhythm and Melatonin:
Our skin naturally makes vitamin D through exposure to the sun. But sun exposure seems to be a double-edged sword these days, with UV light giving us vitamin D as well as increasing our risk for cancer. It makes you wonder why all of our ancestors didn’t end up with skin cancer without a handy bottle of sunscreen available.

Turns out that our modern lifestyle with light at night (TV’s, tablets, phones, and LED light bulbs) has decreased our melatonin production. Melatonin at the right time plays a big role in both our circadian rhythm and our skins natural ability to withstand UV rays without creating skin cancer. Blocking blue light wavelengths at night increases melatonin production and should increase our skin’s ability to utilize UV rays for vitamin D production without the harmful effects. [ref]  Read more about melatonin production, genetics, and blue light.

In addition to light at night, the time at which you eat also influences the circadian rhythm of your genes. A recent study showed that mice that eat at the wrong time (equivalent to humans eating at night) had increased skin damage from UV light. Basically, eating at the wrong time-shifted the phase of the circadian rhythm of skin genes to where UV damage would be less of a problem at night rather than during the day… and the sun doesn’t shine at night! So an easy ‘lifehack’ here would be to eat dinner earlier in the evening and don’t snack at night.

Food and Supplements:
Currently, in the US and Canada, vitamin D is added to milk.  Fatty fish, such as salmon, tuna, and mackerel, are also good sources of vitamin D.  Some types of mushrooms, when exposed to UV light, also contain vitamin D (as D2).

There are many vitamin D supplements available at stores and online.  Keep in mind that vitamin D is fat soluble and supplements usually contain oil such as soybean oil, which you may want to avoid. Again, the jury seems to still be out when it comes to a definitive recommendation on how much vitamin D is needed; you may find that your sun exposure is enough to keep your levels high enough.

Gut Microbiome:
The VDR gene, as well as other genes associated with vitamin D, plays a role in gut microbiome diversity.  VDR knockout mice had a 42% decrease in microbiome diversity index. That is pretty huge. Parabacteroides is one of the taxa that is affected by VDR genetic variants; it feeds on resistant starch, so adding in fiber and resistant starch might help encourage that microbe if you have decreased VDR. [ref]

Testing Vitamin D levels:
If you haven’t recently tested your vitamin D level, it is an easy and fairly inexpensive blood test.  If you are in the US, there are lots of online sites where you can order lab tests without doctor’s order such as UltaLabs.

 



Author Information:   Debbie Moon
Debbie Moon is the founder of Genetic Lifehacks. She holds a Master of Science in Biological Sciences from Clemson University. Debbie is a science communicator who is passionate about explaining evidence-based health information. Her goal with Genetic Lifehacks is to bridge the gap between scientific research and the lay person's ability to utilize that information. To contact Debbie, visit the contact page.