1. Genetic Variation of the Vitamin D Binding Protein Affects Vitamin D Status and Response to Supplementation in Infants
- Author
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Heli Viljakainen, Outi Mäkitie, Jenni Rosendahl, Otto Helve, Minna Pekkinen, Laura Koljonen, Timo Hytinantti, Sture Andersson, Helena Hauta-alus, Elisa Holmlund-Suila, Saara Valkama, Maria Enlund-Cerullo, HUSLAB, Children's Hospital, HUS Children and Adolescents, University of Helsinki, CAMM - Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, Clinicum, Research Programs Unit, Staff Services, Department of Food and Nutrition, University Management, and Lastentautien yksikkö
- Subjects
Male ,0301 basic medicine ,D INSUFFICIENCY ,Vitamin D-binding protein ,Endocrinology, Diabetes and Metabolism ,Clinical Biochemistry ,DETERMINANTS ,VARIANTS ,PHENOTYPE ,Biochemistry ,chemistry.chemical_compound ,0302 clinical medicine ,Endocrinology ,Vitamin D ,Cholecalciferol ,25(OH)D ,Vitamin D-Binding Protein ,3. Good health ,Online Only ,Female ,Vitamin ,medicine.medical_specialty ,Genotype ,030209 endocrinology & metabolism ,Context (language use) ,Single-nucleotide polymorphism ,Polymorphism, Single Nucleotide ,D DEFICIENCY ,03 medical and health sciences ,Double-Blind Method ,GC-GLOBULIN ,Internal medicine ,medicine ,Vitamin D and neurology ,Humans ,GENOME-WIDE ASSOCIATION ,Alleles ,business.industry ,Biochemistry (medical) ,Infant, Newborn ,Infant ,PREVENTION ,Minor allele frequency ,030104 developmental biology ,Haplotypes ,chemistry ,Pharmacogenetics ,3121 General medicine, internal medicine and other clinical medicine ,1182 Biochemistry, cell and molecular biology ,Calcifediol ,SERUM 25-HYDROXYVITAMIN D ,3111 Biomedicine ,business - Abstract
ContextSingle 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.ObjectiveTo study GC genotype–related differences in 25OHD concentrations and the response to supplementation during a vitamin D intervention study in infants.DesignIn 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 Measures25OHD measured in cord blood at birth and at 12 and 24 months during intervention.ResultsA 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.ConclusionsIn infants, vitamin D binding protein genotype affects 25OHD concentration and efficiency of high-dose vitamin D3 supplementation.
- Published
- 2019
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