Institute for Medical Statistics and Informatics, Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
Department of Internal Medicine, Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, USA.
Biol Sex Differ. 2020 Jul 6;11(1):36. doi: 10.1186/s13293-020-00313-8.
Studies have recently examined the role of epigenetic mechanisms in preeclampsia pathophysiology. One commonly examined epigenetic process is DNA methylation. This heritable epigenetic marker is involved in many important cellular functions. The aim of this study was to establish the association between DNA methylation and preeclampsia and to critically appraise the roles of major study characteristics that can significantly impact the association between DNA methylation and preeclampsia.
A systematic review was performed by searching PubMed, Web of Science, and EMBASE for original research articles published over time, until May 31, 2019 in English. Eligible studies compared DNA methylation levels in pregnant women with vs. without preeclampsia. Ninety articles were included. Epigenome-wide studies identified hundreds of differentially methylated places/regions in preeclamptic patients. Hypomethylation was the predominant finding in studies analyzing placental tissue (14/19), while hypermethylation was detected in three studies that analyzed maternal white blood cells (3/3). In candidate gene studies, methylation alterations for a number of genes were found to be associated with preeclampsia. A greater number of differentially methylated genes was found when analyzing more severe preeclampsia (70/82), compared to studies analyzing less severe preeclampsia vs. controls (13/27). A high degree of heterogeneity existed among the studies in terms of methodological study characteristics including design (study design, definition of preeclampsia, control group, sample size, confounders), implementation (biological sample, DNA methylation method, purification of DNA extraction, and validation of methylation), analysis (analytical method, batch effect, genotyping, and gene expression), and data presentation (methylation quantification measure, measure of variability, reporting). Based on the results of this review, we provide recommendations for study design and analytical approach for further studies.
The findings from this review support the role of DNA methylation in the pathophysiology of preeclampsia. Establishing field-wide methodological and analytical standards may increase value and reduce waste, allowing researchers to gain additional insights into the role of DNA methylation in the pathophysiology of preeclampsia.
最近的研究探讨了表观遗传机制在子痫前期病理生理学中的作用。一个常见的表观遗传过程是 DNA 甲基化。这种可遗传的表观遗传标记参与了许多重要的细胞功能。本研究的目的是建立 DNA 甲基化与子痫前期之间的关联，并批判性地评价可能显著影响 DNA 甲基化与子痫前期之间关联的主要研究特征的作用。
通过检索 PubMed、Web of Science 和 EMBASE，对发表于过去的、截至 2019 年 5 月 31 日的英文原创研究文章进行了系统评价。符合条件的研究比较了子痫前期孕妇与非子痫前期孕妇的 DNA 甲基化水平。共纳入 90 篇文章。全基因组研究鉴定了子痫前期患者数百个差异甲基化的位置/区域。在分析胎盘组织的研究中（19 篇中的 14 篇）发现低甲基化是主要发现，而在分析母亲白细胞的三项研究中（3 篇中的 3 篇）则检测到高甲基化。在候选基因研究中，发现许多基因的甲基化改变与子痫前期有关。在分析更严重的子痫前期时，发现更多的差异甲基化基因（70/82），而在分析较不严重的子痫前期与对照组时，发现 13/27 个基因。研究在方法学研究特征方面存在很大的异质性，包括设计（研究设计、子痫前期定义、对照组、样本量、混杂因素）、实施（生物样本、DNA 甲基化方法、DNA 提取纯化、甲基化验证）、分析（分析方法、批次效应、基因分型、基因表达）和数据呈现（甲基化定量测量、变异性测量、报告）。基于本综述的结果，我们为进一步研究提供了研究设计和分析方法的建议。
本综述的研究结果支持 DNA 甲基化在子痫前期病理生理学中的作用。建立领域广泛的方法学和分析标准可以增加价值，减少浪费，使研究人员能够进一步深入了解 DNA 甲基化在子痫前期病理生理学中的作用。
