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

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.

Association Between Vitamin D-Binding Protein (Vdbp) Gene Polymorphism and Vitamin D Status in Young Children

“…Vitamin D-binding protein (VDBP, vitamin D-binding protein, GS-globulin), which was identified in 1959, is one of the most common whey proteins and provides transport of about 90 % of circulating metabolites of vitamin D [1,2] located in chromosome 4q11-q13 and consists of 13 exons encoding 474 amino acid sequences [3]. VDBP is one of the main genes in which mutations can affect the concentration of 25 (OH) D [4][5][6]. This is due to the fact that most vitamin D circulates in the blood in combination with GC (VDBP), which is present in plasma, cerebrospinal fluid, and in the process of metabolism is associated with various forms of vitamin D [7].…”

The role of DBP gene polymorphisms in the prevalence of new coronavirus disease 2019 infection and mortality rate

“…To test this hypothesis and to limit confounding bias (latitude, etc), we focused on the countries whose DBP polymorphisms at rs7041 and rs4588 loci were defined and the allele frequencies reported in five cohort and two systematic review and meta‐analysis studies 8‐15 . We searched the literature for DBP gene polymorphism in each country.…”

Genomics in Personalized Nutrition: Can You “Eat for Your Genes”?

“…All three haplotypes are relatively common in populations of European descent, but among Africans, GC1f is very common (>80% allele frequency) while GC2 is rare [ 103 , 104 ]. Many studies have found lower serum concentrations of 25(OH)D in carriers of one or more GC2 alleles with GC2/GC2 homozygotes being most at risk of deficiency (see, for example, [ 105 , 106 , 107 ]). Enlund-Cerullo et al studied these two SNPs, along with several others, separately and in combination, in a trial of vitamin D supplementation in infants of European descent [ 107 ].…”

“…Many studies have found lower serum concentrations of 25(OH)D in carriers of one or more GC2 alleles with GC2/GC2 homozygotes being most at risk of deficiency (see, for example, [ 105 , 106 , 107 ]). Enlund-Cerullo et al studied these two SNPs, along with several others, separately and in combination, in a trial of vitamin D supplementation in infants of European descent [ 107 ]. They found that the rs4588 A/A genotype and the GC2/GC2 diplotype were both associated with low serum levels of 25(OH)D at birth; these variants and the rs7041 G/G genotype were also less responsive to vitamin D supplementation [ 107 ].…”

“…Enlund-Cerullo et al studied these two SNPs, along with several others, separately and in combination, in a trial of vitamin D supplementation in infants of European descent [ 107 ]. They found that the rs4588 A/A genotype and the GC2/GC2 diplotype were both associated with low serum levels of 25(OH)D at birth; these variants and the rs7041 G/G genotype were also less responsive to vitamin D supplementation [ 107 ]. Given these results, GC2 carriers (and especially GC2 homozygotes) are likely to benefit most from monitoring of serum vitamin D levels, with supplementation as needed.…”