A variant in CYP2R1 predicts circulating vitamin D levels after supplementation with high-dose of vitamin D in healthy adolescent girls

J Cell Physiol. 2019 Aug;234(8):13977-13983. doi: 10.1002/jcp.28083. Epub 2019 Jan 9.

Abstract

Aim: The determinants of serum vitamin D seems to be the environmental factors (dietary and supplementary intake and exposure to ultraviolet light) and genetic factors. We aimed to study the relationship between a vitamin D-associated genetic polymorphism and serum 25(OH)D concentrations in healthy adolescent girls in Iran, and its effects on a high-dose supplement of vitamin D.

Material and method: A total of 616 healthy adolescent girls with mean age 15 received 50,000 IU of vitamin D3 weekly over 9 weeks. Serum vitamin D levels and other metabolic factors were measured at baseline and after the intervention. The genotyping of the CYP2R1 variant (rs10741657) was performed by TaqMan genotyping assays.

Results: Regardless of the genetic background, at baseline, 87% of adolescent girls were vitamin D deficient (serum 25(OH)D level < 50 nmol/l). High-dose supplementation with VitD reduced the proportion of girls who were deficient substantially to about 24%. The genetic analysis revealed that although at baseline there was not a gene-vitamin D association ( p trend = 0.1), the response to supplementation appeared to be modulated by this variant ( p trend < 0.001). However, other anthropometric and biochemical measures were not affected by this intervention, over this short period. Serum 25(OH)D was increased in all participants although the carriers of the minor A allele seemed to be better responders so that the percentages of the change serum vitamin D in the holder of AA and AG genotypes were 539.4 ± 443.1 and 443.7 ± 384.6, respectively, compared with those with common GG genotype (363.3 ± 354.0). Our regression analysis revealed that the probability of an increase in serum 25(OH)D in a participant with AA genotype was 2.5-fold greater than those with a GG genotype (OR = 2.5 (1.4-4.4); p value = 0.002).

Conclusion: Based on our findings, it appears that the rs10741657 variant of the CYP2R1 gene modulates the response to high-dose of vitamin D supplementation.

Keywords: CYP2R1; rs10741657; supplementation; vitamin D.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Cholestanetriol 26-Monooxygenase / genetics*
  • Cytochrome P450 Family 2 / genetics*
  • Dietary Supplements*
  • Female
  • Genetic Variation*
  • Humans
  • Metabolomics
  • Polymorphism, Single Nucleotide / genetics
  • Vitamin D / analogs & derivatives
  • Vitamin D / blood*

Substances

  • Vitamin D
  • 25-hydroxyvitamin D
  • Cytochrome P450 Family 2
  • CYP2R1 protein, human
  • Cholestanetriol 26-Monooxygenase