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J Clin Endocrinol Metab. 2019 Jul 31. pii: jc.2019-00630. doi: 10.1210/jc.2019-00630. [Epub ahead of print]

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

Author information

1
Children's Hospital, Pediatric Research Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
2
Folkhälsan Research Center, Helsinki, Finland.
3
Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Finland.
4
The Department of Food and Nutrition, University of Helsinki, Helsinki, Finland.
5
Center for Molecular Medicine, Karolinska Institutet, and Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden.

Abstract

CONTEXT:

Single nucleotide polymorphisms (SNPs) of the vitamin D binding protein encoding 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 response to supplementation during a vitamin D intervention study in infants.

DESIGN:

In this randomized controlled trial, healthy term infants received 10 or 30 μg vitamin D3/day 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:

Altogether 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 p<0.043), with the exception of rs7041 which did not affect 25OHD at birth. In the high-dose supplementation group, receiving 30 μg vitamin D3/day, but not in those receiving 10 µg/day, genotype of rs2282679, rs4588 and rs7041, diplotype and Haplo3SNP significantly affected intervention response (repeated measurement analysis of covariance pinteraction <0.019). Minor allele homozygotes had lower 25OHD concentrations and smaller increase in 25OHD throughout intervention.

CONCLUSIONS:

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

PMID:
31365099
DOI:
10.1210/jc.2019-00630

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