Genetic Variation Of The Vitamin D Binding Protein Affects Vitamin D Status And Response To Supplementation In Infants

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 D-3 (10 or 30 mu g/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 (Haplo(3SNP)) and of all four SNPs (Haplo(4SNP)) 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 mu g/d vitamin D-3, but not in those receiving 10 mu g/d, genotype of rs2282679, rs4588, and rs7041; diplotype; and Haplo(3SNP) significantly affected intervention response (repeated measurement ANCOVA P-interaction < 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 D-3 supplementation.