Maria Enlund-Cerullo1,2,3, Laura Koljonen2,3, Elisa Holmlund-Suila1,3, Helena Hauta-Alus1,3, Jenni Rosendahl1,3, Saara Valkama1,3, Otto Helve1, Timo Hytinantti1, Heli Viljakainen2,4, Sture Andersson1, Outi Mäkitie1,2,3,5, Minna Pekkinen1,2,3. 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, 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 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.
RCT Entities:
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.
Authors: Cora M Best; Leila R Zelnick; Kenneth E Thummel; Simon Hsu; Christine Limonte; Ravi Thadhani; Howard D Sesso; JoAnn E Manson; Julie E Buring; Samia Mora; I-Min Lee; Nancy R Cook; Georgina Friedenberg; Heike Luttmann-Gibson; Ian H de Boer; Andrew N Hoofnagle Journal: J Clin Endocrinol Metab Date: 2022-01-18 Impact factor: 6.134
Authors: Veronica A Mullins; William Bresette; Laurel Johnstone; Brian Hallmark; Floyd H Chilton Journal: Nutrients Date: 2020-10-13 Impact factor: 5.717
Authors: Max Mimpen; Linda Rolf; Geert Poelmans; Jody van den Ouweland; Raymond Hupperts; Jan Damoiseaux; Joost Smolders Journal: PLoS One Date: 2021-12-02 Impact factor: 3.240
Authors: Christine A Simpson; Jane H Zhang; Dirk Vanderschueren; Lei Fu; Teresita C Pennestri; Roger Bouillon; David E C Cole; Thomas O Carpenter Journal: Eur J Endocrinol Date: 2021-07-07 Impact factor: 6.558