COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark.
Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Pediatr Allergy Immunol. 2021 May;32(4):679-689. doi: 10.1111/pai.13453. Epub 2021 Feb 20.
Randomized controlled trials (RCTs) suggest a protective effect of high-dose vitamin D supplementation in pregnancy on offspring risk of persistent wheeze, but only in some individuals, which might be explained by variations in vitamin D pathway genes. This study aimed to investigate the effect of vitamin D supplementation by maternal and offspring vitamin D receptor (VDR) genotype and GC genotype, encoding vitamin D binding protein (VDBP), in two RCTs.
In the Copenhagen Prospective Studies on Asthma in Childhood (COPSAC ) RCT, we analyzed the effect of high-dose vitamin D during pregnancy on the risk of persistent wheeze age 0-3 years by variants in single nucleotide polymorphisms (SNPs) in VDR (rs1544410, rs2228570, rs7975128, rs7975232) and GC (rs4588, rs7041). Replication was sought in the Vitamin D Antenatal Asthma Reduction Trial (VDAART).
In COPSAC , VDR SNP rs1544410 influenced the effect of high-dose vitamin D: maternal P = .049 and child P = .001, with the largest effect in offspring from mothers with TT genotype: hazard ratio (95% CI), 0.26 (0.10-0.68), P = .006, and no effect among CT or CC genotypes: 0.85 (0.48-1.51), P = .58 and 0.94 (0.47-1.89), P = .87, respectively. However, these findings were not replicated in VDAART. There was no significant effect modification from maternal or offspring GC genotype in either COPSAC or VDAART: all P ≥ .17.
We found that the effect of high-dose vitamin D supplementation during pregnancy on offspring risk of persistent wheeze was significantly influenced by VDR genotype in the COPSAC RCT, but not VDAART, which may be due to population differences.
随机对照试验（RCTs）表明，妊娠期间高剂量维生素 D 补充可降低后代持续性喘息的风险，但仅在某些人群中有效，这可能与维生素 D 途径基因的变异有关。本研究旨在通过母体和子代维生素 D 受体（VDR）基因型和编码维生素 D 结合蛋白（VDBP）的 GC 基因型，在两项 RCT 中研究维生素 D 补充的效果。
在哥本哈根儿童哮喘前瞻性研究（COPSAC）RCT 中，我们分析了 VDR（rs1544410、rs2228570、rs7975128、rs7975232）和 GC（rs4588、rs7041）单核苷酸多态性（SNP）变异对妊娠期间高剂量维生素 D 对 0-3 岁持续性喘息风险的影响。在维生素 D 产前哮喘减少试验（VDAART）中寻求了复制。
在 COPSAC 中，VDR SNP rs1544410 影响了高剂量维生素 D 的效果：母亲 P 为.049，孩子 P 为.001，TT 基因型母亲的后代效果最大：危险比（95%CI），0.26（0.10-0.68），P 为.006，而 CT 或 CC 基因型则没有影响：0.85（0.48-1.51），P 为.58 和 0.94（0.47-1.89），P 为.87。然而，这些发现并未在 VDAART 中得到复制。在 COPSAC 或 VDAART 中，母体或子代 GC 基因型均未引起明显的效应修饰：所有 P 均≥.17。
我们发现，妊娠期间高剂量维生素 D 补充对后代持续性喘息风险的影响在 COPSAC RCT 中受 VDR 基因型的显著影响，但在 VDAART 中则不受影响，这可能是由于人群差异所致。
