Genetic Variation of the Vitamin D Binding Protein Affects Vitamin D Status and Response to Supplementation in Infants

J Clin Endocrinol Metab. 2019 Nov 1;104(11):5483-5498. doi: 10.1210/jc.2019-00630.

Abstract

Context: Single nucleotide polymorphisms (SNPs) of the vitamin D binding protein encoding the GC (group component) gene affect 25-hydroxyvitamin D (25OHD) concentrations, but their influence on vitamin D status and response to vitamin D supplementation in infants is unknown.

Objective: To study GC genotype-related differences in 25OHD concentrations and the response to supplementation during a vitamin D intervention study in infants.

Design: In this randomized controlled trial, healthy term infants received vitamin D3 (10 or 30 μg/d) from 2 weeks to 24 months of age. GC SNPs rs2282679, rs4588, rs7041, and rs1155563 were genotyped. rs4588/7041 diplotype and haplotypes of rs2282679, rs4588, and rs7041 (Haplo3SNP) and of all four SNPs (Haplo4SNP) were determined.

Main outcome measures: 25OHD measured in cord blood at birth and at 12 and 24 months during intervention.

Results: A total of 913 infants were included. Minor allele homozygosity of all studied GC SNPs, their combined haplotypes, and rs4588/rs7041 diplotype 2/2 were associated with lower 25OHD concentrations at all time points in one or both intervention groups [analysis of covariance (ANCOVA) P < 0.043], with the exception of rs7041, which did not affect 25OHD at birth. In the high-dose supplementation group receiving 30 μg/d vitamin D3, but not in those receiving 10 µg/d, genotype of rs2282679, rs4588, and rs7041; diplotype; and Haplo3SNP significantly affected intervention response (repeated measurement ANCOVA Pinteraction < 0.019). Minor allele homozygotes had lower 25OHD concentrations and smaller increases in 25OHD throughout the intervention.

Conclusions: In infants, vitamin D binding protein genotype affects 25OHD concentration and efficiency of high-dose vitamin D3 supplementation.

Trial registration: ClinicalTrials.gov NCT01723852.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Cholecalciferol / administration & dosage*
  • Double-Blind Method
  • Female
  • Genotype*
  • Haplotypes
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Pharmacogenetics
  • Polymorphism, Single Nucleotide*
  • Vitamin D / analogs & derivatives*
  • Vitamin D / blood
  • Vitamin D-Binding Protein / genetics*

Substances

  • Vitamin D-Binding Protein
  • Vitamin D
  • Cholecalciferol
  • 25-hydroxyvitamin D

Associated data

  • ClinicalTrials.gov/NCT01723852