Children's Hospital, Pediatric Research Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
Folkhälsan Research Center, Helsinki, Finland.
J Clin Endocrinol Metab. 2019 Nov 1;104(11):5483-5498. doi: 10.1210/jc.2019-00630.
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.
To study GC genotype-related differences in 25OHD concentrations and the response to supplementation during a vitamin D intervention study in infants.
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.
25OHD measured in cord blood at birth and at 12 and 24 months during intervention.
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.
In infants, vitamin D binding protein genotype affects 25OHD concentration and efficiency of high-dose vitamin D3 supplementation.
维生素 D 结合蛋白编码 GC（群组成分）基因的单核苷酸多态性（SNPs）会影响 25-羟基维生素 D（25OHD）浓度，但它们对婴儿维生素 D 状态和对维生素 D 补充的反应的影响尚不清楚。
研究 GC 基因型相关的 25OHD 浓度差异以及在婴儿维生素 D 干预研究中对补充的反应。
在这项随机对照试验中，健康的足月婴儿从 2 周龄到 24 月龄接受维生素 D3（10 或 30μg/d）。对 GC SNPs rs2282679、rs4588、rs7041 和 rs1155563 进行基因分型。确定 rs4588/7041 二倍体型和 rs2282679、rs4588 和 rs7041（Haplo3SNP）以及所有四个 SNPs（Haplo4SNP）的单倍型。
出生时和干预期间 12 个月和 24 个月时脐带血中的 25OHD 测量值。
共纳入 913 名婴儿。所有研究的 GC SNPs、它们的组合单倍型以及 rs4588/rs7041 二倍体型 2/2 的次要等位基因纯合性在一个或两个干预组的所有时间点均与 25OHD 浓度较低相关[协方差分析（ANCOVA）P<0.043]，但 rs7041 除外，其在出生时不影响 25OHD。在接受 30μg/d 维生素 D3 高剂量补充的组中，但在接受 10μg/d 维生素 D3 补充的组中，rs2282679、rs4588 和 rs7041 的基因型、二倍体型和 Haplo3SNP 显著影响干预反应（重复测量 ANCOVA P 交互作用<0.019）。次要等位基因纯合子在整个干预过程中 25OHD 浓度较低，25OHD 增加较小。
在婴儿中，维生素 D 结合蛋白基因型影响 25OHD 浓度和高效的大剂量维生素 D3 补充。
