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CYP24A1

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Cytochrome P450 24A1 (CYP24A1) is an enzyme which is encoded for by the gene CYP24A1. Present in the mitochondria of all cells CYP24A1 converts the bioactive form of vitamin D, calcitriol, into the inactive form calcitroic acid, which is the excreted from the body. Calcitriol binds with vitamin D receptor (VDR) which leads to an increase in calcium uptake from the gut, which is required for bone formation, muscle function and numerous other processes in the body. CYP24A1 is responsible for regulating the levels of calcitriol preventing an over absorption of calcium 1,2.

C552T

Longevity
rsID Number Major Allele Minor Allele Minor Allele Frequency (%) Major Amino Acid Minor Amino Acid
rs2296241 g a 49 Ala Ala

Risk Description

The ‘A’ allele of the SNP C552T in the CYP24A1 gene is associated with an increased risk of prostate or oral cancer. However, it is not currently known if this is driven through the occurrence of vitamin D deficiency, or how the ‘A’ allele of C552T could lead to this deficiency. It is possible to hypothesize, based on normal CYP24A1 function, that in those with the ‘A’ allele CYP24A1 activity is increased, meaning bioactive vitamin D, calcitriol, is more rapidly converted into calcitroic acid and excreted. This rapid conversion leads to the development of vitamin D deficiency and the increase in cancer risk 3,4.

Direct Nutrients:*

Ingredient Active Ingredient Effect
Vitamin D Calcitriol

CYP24A1 is responsible for breaking down bioactive vitamin D, calcitriol, into calcitroic acid which is then excreted from the body. For those with the ‘A’ allele of C552T, which may be associated with increased calcitriol breakdown, and therefore vitamin D deficiency, supplementation with the bioactive form of calcitriol may help ensure that appropriate vitamin D levels are maintained 4.

This may reduce the risk of cancers associated with the ‘A’ allele of C552T. Additionally, given that the majority of us are vitamin D deficient, supplementation is usually to be recommended to ensure that all cellular activities dependent on vitamin D can proceed normally 5.

Discuss this information with your doctor before taking any course of action.

T1236+198C

Longevity
rsID Number Major Allele Minor Allele Minor Allele Frequency (%)
rs1570669 a g 47

Risk Description

The ‘G’ allele of the SNP T1236+198C in the CYP24A1 gene is associated with an increased risk of breast and colon cancer. However, it is not currently known if this is driven through the occurrence of vitamin D deficiency, or how the ‘G’ allele of T1236+198C could lead to this deficiency. It is possible to hypothesize, based on normal CYP24A1 function, that in those with the ‘G’ allele CYP24A1 activity is increased, meaning bioactive vitamin D, calcitriol, is more rapidly converted into calcitroic acid and excreted. This rapid conversion leads to the development of vitamin D deficiency and the increase in cancer risk. The ’G’ allele of T1236+198C was associated with a very mild reduction in calcium uptake, however no impact on bone health was observed 68.

Direct Nutrients:*

Ingredient Active Ingredient Effect
Vitamin D Calcitriol

CYP24A1 breaks down bioactive vitamin D, calcitriol, into calcitroic acid for excretion from the body. For those with the ‘G’ allele of T1236+198C, which may be associated with increased calcitriol breakdown, and therefore vitamin D deficiency, supplementation with the bioactive form of calcitriol may help ensure that appropriate vitamin D levels are maintained. Which may reduce the risk of cancer associated with the ‘G’ allele of C552T. Additionally, given that the majority of us are vitamin D deficient anyway supplementation is to be recommended to ensure that cellular activities dependent on vitamin D can proceed normally 5.

Discuss this information with your doctor before taking any course of action.

G-1400A

Brain Health
rsID Number Major Allele Minor Allele Minor Allele Frequency (%)
rs2248359 c t 45

Risk Description

The ‘C’ allele of the SNP G-1400A in the CYP24A1 has been linked with the development of multiple sclerosis (MS). In those with the ‘C’ allele CYP24A1 expression was significantly increased in the frontal cortex of the brain, a region very important in the development of MS. CYP24A1 functions to convert bioactive vitamin D, calcitriol, into calcitroic acid for excretion from the body. Therefore, when it is over-expressed in the frontal cortex of the brain, vitamin D in the frontal cortex is more rapidly broken down, leading to a tissue specific vitamin D deficiency 9.

Direct Nutrients:*

Ingredient Active Ingredient Effect
Vitamin D Calcitriol

CYP24A1 is responsible for breaking down bioactive vitamin D, calcitriol, into calcitroic acid for excretion from the body. For those with the ‘C’ allele of G-1400A, which may be associated with increased calcitriol breakdown in the frontal cortex of the brain, and therefore vitamin D deficiency, supplementation with the bioactive form of calcitriol may help ensure that appropriate vitamin D levels are maintained. Which may reduce the risk of multiple sclerosis associated with the ‘C’ allele of G-1400A. Importantly, given that the ‘C’ allele of G-1400A is associated with altered expression only in the frontal cortex of the brain, it may not be possible to detect vitamin D deficiencies through typical blood tests. Given that the majority of us are vitamin D deficient anyway supplementation is to be recommended to ensure that cellular activities dependent on vitamin D can proceed normally 5.

Discuss this information with your doctor before taking any course of action.

Dr. Aaron Gardner, BSc, MRes, PhD

Dr. Aaron Gardner, BSc, MRes, PhD is a life-scientist with a strong background in genetics and medical research, and the developing fields of personalized medicine and nutrition. Read his full bio here.
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