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.

Context Phosphate homeostasis and its modifiers in early childhood are inadequately characterized. Objective To determine physiological plasma phosphate concentration and modifying factors in healthy infants at 12 to 24 months of age. Design This study included 525 healthy infants (53% girls), who participated in a randomized vitamin D intervention (VIDI) trial and received daily vitamin D3 supplementation of either 10 or 30 μg from age two weeks to 24 months. Biochemical parameters were measured at 12 and 24 months. Dietary phosphate intake was determined at 12 months. Main Outcome Measures Plasma phosphate concentrations at 12 and 24 months of age. Results Mean (SD) phosphate concentration decreased from 12 months (1.9±0.15 mmol/L) to 24 months (1.6±0.17 mmol/L) of age (p&lt;0.001 for repeated measurements). When adjusted by covariates, such as body size, creatinine, 25OHD, intact and C-terminal FGF23, mean plasma phosphate was higher in boys than girls during follow-up (p=0.019). Phosphate concentrations were similar in the vitamin D intervention groups (p&gt;0.472 for all). Plasma iron was associated positively with plasma phosphate at both time points (B, 0.006 and 0.005, 95% CI 0.004 to 0.009 and 0.002 to 0.008, p&lt;0.001 at both time points, respectively). At 24 months of age, the main modifier of phosphate concentration was plasma creatinine (B, 0.007, 95% CI 0.003 to 0.011, p&lt;0.001). Conclusion Plasma phosphate concentration decreased from age 12 to 24 months. In infants and toddlers, the strongest plasma phosphate modifiers were sex, iron, and creatinine, whereas vitamin D supplementation did not modify phosphate concentrations.