维生素 D 及其代谢通路基因多态性与早产的相关性研究。

Association of vitamin D and gene variants in the vitamin D metabolic pathway with preterm birth.

机构信息

Departments of Public Health and Anesthesiology, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China; Department of Epidemiology & Health Statistics, School of Public Health, School of Medicine, Zhejiang University, Hangzhou, China; Tencent Jarvis Lab, Shenzhen, China.

出版信息

Nutrition. 2021 Sep;89:111349. doi: 10.1016/j.nut.2021.111349. Epub 2021 May 24.

DOI:10.1016/j.nut.2021.111349

PMID:34217944

Abstract

OBJECTIVES

The aim of this study was to explore the association of vitamin D (VitD) levels during pregnancy and its metabolic pathway genes with the risk for preterm birth (PTB) among pregnant women in southeast China.

METHODS

This study was conducted in Zhoushan Maternal and Child Health Hospital, Zhejiang, from August 2011 to May 2018. Plasma 25-hydroxyvitamin vitamin D [25(OH)D] levels in three trimesters and single-nucleotide morphisms in the VitD metabolic pathway were measured. Relevant information was collected using questionnaires and an electronic medical recorder system. Multiple statistical methods including linear regression, logistic regression, and crossover analysis were applied.

RESULTS

The prospective cohort study included 3465 pregnant women, of which 202 were PTB (week of gestation at delivery: 33.38 ± 4.05), accounting for 5.8%. After adjusting for potential confounders, VitD sufficiency (≥30 ng/mL) in the second and third trimesters was associated with longer gestational age at delivery compared with VitD deficiency (<20 ng/mL). However, no significant association was found between VitD with the risk for PTB. rs7041, rs10210408, and rs2228171 were associated with gestational week and the risk for PTB. Significant associations were found of rs10210408, rs2209314, rs1155563, rs2544381 and the status of VitD in the second and third trimester with the gestational week. We also found that rs7041 and VitD in the second trimester might exert interaction on gestational week and the risk for PTB (P = 0.038; P = 0.019); rs16846876 and VitD in the second trimester might exert interaction on gestational week (P = 0.024); rs4334089 and VitD in the third trimester might exert interaction on gestational week (P = 0.024). Similar results were found when we tested pregnant women's plasma 25(OH)D in the first and second trimesters.

CONCLUSIONS

Women with VitD deficiency were associated with shorter gestational weeks. Single-nucleotide morphisms in VitD metabolic pathway genes were significantly associated with gestation week and the risk for PTB, mainly in vitamin D-binding protein (GC) and low-density lipoprotein-related protein 2 (LRP2)genes. Additionally, maternal VitD with GC gene and maternal VitD with vitamin D receptor (VDR) gene might exert interactions on the risk for PTB.

摘要

目的

本研究旨在探讨中国东南部孕妇妊娠期间维生素 D（VitD）水平及其代谢途径基因与早产（PTB）风险的关系。

方法

本研究于 2011 年 8 月至 2018 年 5 月在浙江舟山妇幼保健院进行。检测了妊娠三个时期的血浆 25-羟维生素 D [25(OH)D]水平和 VitD 代谢途径中的单核苷酸多态性。使用问卷和电子病历系统收集相关信息。应用线性回归、逻辑回归和交叉分析等多种统计方法。

结果

这项前瞻性队列研究纳入了 3465 名孕妇，其中 202 例发生早产（分娩时孕周：33.38±4.05），占 5.8%。调整潜在混杂因素后，与 VitD 缺乏（<20ng/mL）相比，妊娠第二和第三期 VitD 充足（≥30ng/mL）与分娩时的胎龄较长有关。然而，VitD 与 PTB 风险之间无显著相关性。rs7041、rs10210408 和 rs2228171 与孕周和 PTB 风险相关。rs10210408、rs2209314、rs1155563、rs2544381 和第二和第三孕期 VitD 状态与胎龄之间存在显著关联。我们还发现，rs7041 和第二孕期 VitD 可能对孕周和 PTB 风险有交互作用（P=0.038；P=0.019）；rs16846876 和第二孕期 VitD 可能对孕周有交互作用（P=0.024）；rs4334089 和第三孕期 VitD 可能对孕周有交互作用（P=0.024）。当我们检测孕妇第一和第二孕期的血浆 25(OH)D 时，也得到了类似的结果。

结论

VitD 缺乏的孕妇与较短的胎龄有关。VitD 代谢途径基因中的单核苷酸多态性与胎龄和 PTB 风险显著相关，主要与维生素 D 结合蛋白（GC）和低密度脂蛋白相关蛋白 2（LRP2）基因相关。此外，母体 VitD 与 GC 基因和母体 VitD 与维生素 D 受体（VDR）基因之间可能存在相互作用，影响 PTB 的风险。