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孕18周和28周时无症状孕妇的母血基因表达与自发性早产的关系

Maternal Whole Blood Gene Expression at 18 and 28 Weeks of Gestation Associated with Spontaneous Preterm Birth in Asymptomatic Women.

作者信息

Heng Yujing J, Pennell Craig E, McDonald Sheila W, Vinturache Angela E, Xu Jingxiong, Lee Mary W F, Briollais Laurent, Lyon Andrew W, Slater Donna M, Bocking Alan D, de Koning Lawrence, Olson David M, Dolan Siobhan M, Tough Suzanne C, Lye Stephen J

机构信息

Departments of Obstetrics & Gynaecology and Physiology, University of Toronto, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada.

Department of Pathology, Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, MA, United States of America.

出版信息

PLoS One. 2016 Jun 22;11(6):e0155191. doi: 10.1371/journal.pone.0155191. eCollection 2016.

Abstract

The heterogeneity of spontaneous preterm birth (SPTB) requires an interdisciplinary approach to determine potential predictive risk factors of early delivery. The aim of this study was to investigate maternal whole blood gene expression profiles associated with spontaneous preterm birth (SPTB, <37 weeks) in asymptomatic pregnant women. The study population was a matched subgroup of women (51 SPTBs, 114 term delivery controls) who participated in the All Our Babies community based cohort in Calgary (n = 1878). Maternal blood at 17-23 (sampling time point 1, T1) and 27-33 weeks of gestation (T2) were collected. Total RNA was extracted and microarray was performed on 326 samples (165 women). Univariate analyses determined significant clinical factors and differential gene expression associated with SPTB. Thirteen genes were validated using qRT-PCR. Three multivariate logistic models were constructed to identify gene expression at T1 (Model A), T2 (Model B), and gene expression fold change from T1 to T2 (Model C) associated with SPTB. All models were adjusted for clinical factors. Model C can predict SPTB with 65% sensitivity and 88% specificity in asymptomatic women after adjusting for history of abortion and anaemia (occurring before T2). Clinical data enhanced the sensitivity of the Models to predict SPTB. In conclusion, clinical factors and whole blood gene expression are associated with SPTB in asymptomatic women. An effective screening tool for SPTB during pregnancy would enable targeted preventive approaches and personalised antenatal care.

摘要

自发性早产(SPTB)的异质性需要采用跨学科方法来确定早期分娩的潜在预测风险因素。本研究的目的是调查无症状孕妇中与自发性早产(<37周)相关的母体全血基因表达谱。研究人群是参与卡尔加里基于社区的“我们所有的宝宝”队列研究(n = 1878)的一组匹配女性亚组(51例自发性早产者,114例足月分娩对照者)。在妊娠17 - 23周(采样时间点1,T1)和27 - 33周(T2)采集母体血液。提取总RNA,并对326个样本(165名女性)进行微阵列分析。单因素分析确定了与自发性早产相关的显著临床因素和差异基因表达。使用qRT-PCR对13个基因进行了验证。构建了三个多因素逻辑模型,以识别与自发性早产相关的T1期基因表达(模型A)、T2期基因表达(模型B)以及从T1到T2的基因表达倍数变化(模型C)。所有模型均对临床因素进行了校正。在校正流产史和贫血(发生在T2之前)后,模型C在无症状女性中预测自发性早产的敏感性为65%,特异性为88%。临床数据提高了模型预测自发性早产的敏感性。总之,临床因素和全血基因表达与无症状女性的自发性早产相关。一种有效的孕期自发性早产筛查工具将有助于采取有针对性的预防措施和个性化的产前护理。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/85b3/4917227/6bbf4ddd17ba/pone.0155191.g001.jpg

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