Genetic Variants in CYP2R1, CYP24A1, and VDR Modify the Efficacy of Vitamin D3 Supplementation for Increasing Serum 25-Hydroxyvitamin D Levels in a Randomized Controlled Trial
Genetic Variants in CYP2R1, CYP24A1, and VDR Modify the Efficacy of Vitamin D3 Supplementation for Increasing Serum 25-Hydroxyvitamin D Levels in a Randomized Controlled Trial
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DOI：
10.1210/jc.2014-1389
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发表时间：
2014-10-01
影响因子：
5.8
通讯作者：
Baron, John A.
中科院分区：
文献类型：
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作者：
Barry, Elizabeth L.;Rees, Judy R.;Baron, John A.
背景：充足的血清 25-羟基维生素 D 浓度 [25(OH) D] 是最佳骨骼健康所必需的，低水平与慢性疾病相关。 目的：我们研究了维生素 D 和钙通路基因（GC、DHCR7、CYP2R1、CYP27B1、CYP24A1、 VDR 和 CASR）与 [25(OH)D] 相关，或改变维生素 D-3 补充剂导致的 [25(OH)D] 增加。设计和设置：基线和第 1 年 [25(OH)D] 测量来自在美国 11 个临床中心进行的随机对照试验。参与者：总共 1787 名年龄在 45-75 岁的健康非西班牙裔白人参与者。干预措施： 维生素 D-3（1000 IU/天）、碳酸钙（1200 毫克/天元素），两者或安慰剂。主要结果指标：使用多元线性回归估计基因型主要效应以及与维生素 D-3 治疗的相互作用。结果：基线血清 [25(OH)D] 为 25.4 +/- 8.7 ng/mL（平均值 +/- SD）。 CYP24A1（rs2209314、rs2762939）中的 SNP 与基线水平存在关联，GC 和 CYP2R1 中的 SNP 也得到了证实。 1 年后，维生素 D-3 治疗组的 [25(OH)D] 平均增加 6.1 +/- 8.9 ng/mL，安慰剂组平均减少 1.1 +/- 8.4 ng/mL。补充维生素 D-3 导致的 [25(OH)D] 增加被 CYP2R1 附近的 rs10766197、CYP24A1 附近的 rs6013897 和 VDR 附近的 rs7968585 的基因型修改。结论：补充维生素 D-3 导致的 [25(OH)D] 增加可能会根据常见遗传差异而有所不同。 维生素 D 25-羟化酶 (CYP2R1)、24-羟化酶 (CYP24A1) 和维生素 D 受体 (VDR) 基因。这些发现对于实现最佳维生素 D 状态以及潜在的维生素 D 相关健康结果具有重要意义。
Context: Adequate serum 25-hydroxyvitamin D concentrations, [25(OH) D], are required for optimal bone health, and low levels are associated with chronic diseases.Objective: We investigated whether 41 candidate single nucleotide polymorphisms (SNPs) in vitamin D and calcium pathway genes (GC, DHCR7, CYP2R1, CYP27B1, CYP24A1, VDR, and CASR) are associated with [25(OH) D] or modify the increase in [25(OH) D] from vitamin D-3 supplementation.Design and Setting: Baseline and year 1 [25(OH)D] measurements from a randomized controlled trial conducted at 11 clinical centers in the United States.Participants: A total of 1787 healthy non-Hispanic white participants aged 45-75 years.Interventions: Vitamin D-3 (1000 IU/d), calcium carbonate (1200 mg/d elemental), both, or placebo.Main Outcome Measures: Genotype main effects and interactions with vitamin D-3 treatment estimated using multiple linear regression.Results: The baseline serum [25(OH)D] was 25.4 +/- 8.7 ng/mL (mean +/- SD). Associations with baseline levels were discovered for SNPs in CYP24A1 (rs2209314, rs2762939) and confirmed for SNPs in GC and CYP2R1. After 1 year, [25(OH)D] increased on average by 6.1 +/- 8.9 ng/mL on vitamin D-3 treatment and decreased by 1.1 +/- 8.4 ng/mL on placebo. The increase in [25(OH)D] due to vitamin D-3 supplementation was modified by genotypes at rs10766197 near CYP2R1, rs6013897 near CYP24A1, and rs7968585 near VDR.Conclusions: The increase in [25(OH)D] attributable to vitamin D-3 supplementation may vary according to common genetic differences in vitamin D 25-hydroxylase (CYP2R1), 24-hydroxylase (CYP24A1), and the vitamin Dreceptor(VDR) genes. These findings have implications for achieving optimal vitamin D status and potentially for vitamin D-related health outcomes.