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The Group Specific Component globulin (GC) gene is associated with the synthesis of Group Specific Component globulin (GC), also called the Vitamin D Binding Protein (VDBP), which binds to vitamin D and its plasma metabolites, transporting them to the target tissue. This protein is synthesized by the hepatic parenchymal cells and then secreted into the blood stream. People with the C variant of the gene are shown to be associated with lower vitamin D levels.

Vitamin D is necessary for strong bones and for the absorption of calcium, low level of vitamin D is associated with brittle bones and poor muscle function. Vitamin D deficiency is identified by measuring the level of 25, hydroxy vitamin D in the blood. Increased plasma concentration of plasma 25, hydroxy vitamin D is associated with reduced risk of hypertension.

Does your 23andme, Ancestry DNA, FTDNA raw data have GC gene variant information?

CHIP VersionGC SNPs
23andMe (Use your 23andme raw data to know your GC Variant)
v1 23andmePresent
v2 23andmePresent
v3 23andmePresent
v4 23andmePresent
V5 23andme (current chip)Present
AncestryDNA  (Use your ancestry DNA raw data to know your GC Variant)
v1 ancestry DNAPresent
V2 ancestry DNA (current chip)Present
Family Tree DNA  (Use your FTDNA raw data to know your GC Variant)
OmniExpress microarray chipPresent

Association of Vitamin D concentration and ethnicity:

The GC gene is found to be the strongest genetic determinant of the bioavailability of 25, hydroxy vitamin D. There are three isoforms of GC- GC1F, GC2 and GC1S, they are based on a combination of alleles of the SNPs rs7041 and rs 4588 (rs 2282679 is a close proxy). The isoform GC1F is more common among people with dark skin when compared with people with pale skin. GC2 and GC1S are more common among people with pale skin than among people with dark skin.

The vitamin D binding protein (VDBP) in people with the GC1 isoform has a higher affinity for vitamin D metabolites. This is shown to be associated with variations in the bioavailability of circulating 25, hydroxy vitamin D levels among ethnicities.

Genotype Phenotype
CC[Limitation] More likely to have lower plasma 25, hydroxy vitamin D
CAModerate plasma 25, hydroxy vitamin D
AA[Advantage] More likely to have higher plasma 25, hydroxy vitamin D

How can this information be used?

It is important to choose an appropriate diet based on the genetic profile

For people with C variant (Decrease in plasma 25, hydroxy vitamin D) Likely decrease in plasma 25, hydroxy vitamin D Include 1000 I.U of vitamin D per day Ensure sufficient exposure to sunlight; include enjoyable activities like taking the dog for a walk or a day at the beach with family.
For people with A variant (Normal plasma 25, hydroxy vitamin D) Increased likelihood for normal level of plasma 25, hydroxy vitamin D if the dietary intake is sufficient Spend time outdoors for adequate exposure to sunlight

References:

  1. http://www.sciencedirect.com/science/article/pii/S2213858714701135
  2. https://hyper.ahajournals.org/content/49/5/1063.short
  3. https://www.ncbi.nlm.nih.gov/pubmed/26383826
  4. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3613945/
  5. https://www.ncbi.nlm.nih.gov/pubmed/26275945
  6. https://www.ncbi.nlm.nih.gov/pubmed/21972121?dopt=Abstract
  7. http://thelancet.com/journals/landia/article/PIIS2213-8587(14)70113-5/abstract
  8. http://hyper.ahajournals.org/content/49/5/1063.short

Nutrigenetics, fitness genetics, health genetics are all nascent but rapidly growing areas within human genetics. The information provided herein is based on preliminary scientific studies and it is to be read and understood in that context.”

CASR: The Calcium Gene

The Calcium sensing receptor (CASR) gene is associated with the synthesis of Calcium sensing receptor, a receptor that binds to calcium present in the blood. 

Specific alleles of this gene are known to either increase or decrease the sensitivity to calcium. 

Variants of the gene are shown to be associated with the levels of Calcium, Magnesium, and Phosphate in the blood. 

There are two single nucleotide polymorphisms that have an association with this gene; rs17251221 and rs1801725

The CASR protein is present on the cells of the parathyroid glands, which are associated with the secretion of the parathyroid hormone. 

This hormone transfers calcium from the bone into the blood, with bones acting as storage centers for calcium

When calcium levels are high, the level of parathyroid hormone are low.

This facilitates increased binding of calcium to CASR receptors in kidney.

This ultimately leads to more removal of calcium via kidneys.

Does your 23andMe, Ancestry DNA, FTDNA raw data have CASR gene variant information?

CHIP VersionCASR SNPs
23andMe (Use your 23andme raw data to know your CASR Variant)
v1 23andmePresent
v2 23andmePresent
v3 23andmePresent
v4 23andmePresent
V5 23andme (current chip)Present
AncestryDNA  (Use your ancestry DNA raw data to know your CASR Variant)
v1 ancestry DNAPresent
V2 ancestry DNA (current chip)Present
Family Tree DNA  (Use your FTDNA raw data to know your CASR Variant)
OmniExpress microarray chipPresent

Association with Calcium Levels

In a genome wide association study, it was found that the SNP rs1801725 had a strong association with people of European descent while the SNP rs17251221 had a strong association with people of Indian Asian descent. These two SNPs are found to be in high linkage disequilibrium with each other. Another study showed that people with the G variant (rs17251221) of the gene were associated with increased calcium levels. Each copy of the G allele increases Calcium levels by 0.06 mg/dl.

Association with Magnesium Levels

People with the G variant (rs17251221) of the gene were associated increased magnesium levels in the serum.  

Association with Phosphate Levels

People with the G (rs17251221) variant of the gene are shown to be associated with decreased Phosphate level in the serum. Increased secretion of the parathyroid hormone which results in elevated calcium levels is associated with decreased phosphate levels due to the phosphaturic effect.

Association with multiplicity in calcium nephrothiliasis

People with the G variant were associated with a higher risk of stone multiplicity.

How can this information be used?

It is important to choose an appropriate diet based on the genetic profile.

For people with G (rs17251221) Likely to have increased serum calcium and serum magnesium level. Likely to have decreased serum phosphate level Include 600mg/day of phosphorous from pumpkin seeds, salmon, brazil nuts and shellfish. 
For people with A variant (rs17251221) Likely to have decreased serum calcium and serum magnesium levels Likely to have increased serum phosphate levels Include 40-500mg of calcium per day
For people with T (rs1801725) Likely to have increased serum calcium level
For people with G variant (rs1801725) Likely to have decreased serum calcium Include 40-500mg of calcium per day

References:

  1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2908705/
  2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2951868/
  3. http://csg.sph.umich.edu/yli/publications/pdf/20Kapur2010.pdf
  4. https://www.semanticscholar.org/paper/A-Genetic-Polymorphism-rs17251221-in-the-Calcium-Chou Woon/82bb4ed6982b322b4f8f58ac982ff6fba988ecbb

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