Department of Obstetrics and Gynecology, Division of Obstetrics & Prenatal Medicine, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.
Department of Pathology & Clinical Bioinformatics, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.
Pregnancy Hypertens. 2020 Jan;19:150-158. doi: 10.1016/j.preghy.2020.01.010. Epub 2020 Jan 14.
In a previous mass spectrometry study of our research group, 25 proteins were found to be differentially expressed in cerebrospinal fluid of patients with preeclampsia compared to controls. The objective of the current study was to investigate DNA methylation of the genes encoding for the former mentioned proteins in an independent dataset.
In a nested case-control study of the Rotterdam Periconceptional Cohort, placental tissue, umbilical cord white blood cells and human umbilical vein endothelial cells (HUVEC) were obtained of 13 patients with early-onset preeclampsia, 16 patients with late-onset preeclampsia and 83 normotensive controls (27 patients with fetal growth restriction, 20 patients with spontaneous preterm birth and 36 uncomplicated pregnancies). DNA methylation of 783 CpGs in regions of 25 genes was measured.
DNA methylation of selected candidate genes in early- and late-onset preeclampsia compared to fetal growth restriction, spontaneous preterm birth and uncomplicated controls.
From the 783 CpGs of the 25 selected genes, 15 CpGs were differentially methylated between early-onset preeclampsia and spontaneous preterm birth (3.80 E-5 ≤ p ≤ 0.036). Four CpGs were differentially methylated between early-onset preeclampsia and fetal growth restriction (0.0002 ≤ p ≤ 0.037) and 13 CpGs were differentially methylated between early onset preeclampsia and uncomplicated controls (0.0001 ≤ p ≤ 0.04).
Differences in DNA methylation were found in placental tissue, umbilical cord white blood cells and HUVEC of patients with early onset preeclampsia compared to (un)complicated controls, but not in patients with late-onset preeclampsia. The genes showing the largest differential methylation encode insulin-like growth factor 2 binding protein and receptor and cadherin 13.
在我们研究小组之前的一项质谱研究中，发现与对照组相比，子痫前期患者的脑脊液中有 25 种蛋白质表达差异。本研究的目的是在一个独立的数据集上研究编码这些蛋白质的基因的 DNA 甲基化。
在鹿特丹围孕期队列的巢式病例对照研究中，我们从 13 例早发型子痫前期患者、16 例晚发型子痫前期患者和 83 例正常血压对照组（27 例胎儿生长受限、20 例自发性早产和 36 例无并发症妊娠）中获得胎盘组织、脐带白细胞和人脐静脉内皮细胞（HUVEC）。测量了 25 个基因区域的 783 个 CpG 的 DNA 甲基化。
与胎儿生长受限、自发性早产和无并发症对照组相比，早发型和晚发型子痫前期中选定候选基因的 DNA 甲基化。
在 25 个选定基因的 783 个 CpG 中，早发型子痫前期与自发性早产之间有 15 个 CpG 存在差异甲基化（3.80E-5≤p≤0.036）。早发型子痫前期与胎儿生长受限之间有 4 个 CpG 存在差异甲基化（0.0002≤p≤0.037），早发型子痫前期与无并发症对照组之间有 13 个 CpG 存在差异甲基化（0.0001≤p≤0.04）。
与（无）并发症对照组相比，早发型子痫前期患者的胎盘组织、脐带白细胞和 HUVEC 中存在 DNA 甲基化差异，但晚发型子痫前期患者中没有。表现出最大差异甲基化的基因编码胰岛素样生长因子 2 结合蛋白和受体以及钙黏蛋白 13。
