Department of Obstetrics and Gynecology, Department of Biomedical Research, University Hospital, Inselspital, University of Bern, Friedbuehlstrasse 19, 3010, Bern, Switzerland.
Department for BioMedical Research, Swiss Institute of Bioinformatics, University Hospital, University of Bern, Bern, Switzerland.
Sci Rep. 2022 Nov 18;12(1):19837. doi: 10.1038/s41598-022-24348-6.
Hypertensive disorders of pregnancy (HDP) contribute substantially to perinatal morbidity and mortality. Epigenetic changes point towards cardio-metabolic dysregulation for these vascular disorders. In early pregnancy, epigenetic changes using cell free DNA (cfDNA) are largely unexplored. We aimed to investigate these in HDP between 11 and 14 weeks of gestation by analysis of cfDNA methylation profiles in patients with hypertensive disorders. We identified patients without chronic hypertension but with subsequent development of preeclampsia (PE) (n = 11), with chronic hypertension (HT) but without PE development (n = 14), and lacking both PE and HT (n = 422). We matched patients according to PE risk factors into three groups (n = 5 each group): (1) PE: no HT but PE development, (2) HT: chronic hypertension but no PE and (3) Control: no PE or HT. We successfully optimized our cfDNA isolation process prior to whole genome bisulfite sequencing. Analysis of cfDNA methylation changes indicate a common predisposition in PE and HT groups, chiefly of maternal origin. Assessment of significant differentially methylated regions and annotated genes point towards a common cardiovascular predisposition in preeclampsia and hypertension groups in the first trimester. We postulate the pivotal role of the maternal cardiovascular system in HDP, which is already evident in the first trimester.
妊娠高血压疾病（HDP）对围产期发病率和死亡率有重大影响。表观遗传变化表明这些血管疾病存在心脏代谢失调。在孕早期，游离细胞 DNA（cfDNA）的表观遗传变化在很大程度上尚未被探索。我们旨在通过分析患有高血压疾病的患者的 cfDNA 甲基化谱，研究 11 至 14 周妊娠期间 HDP 中的这些变化。我们鉴定了没有慢性高血压但随后发生子痫前期（PE）的患者（n=11）、有慢性高血压但没有 PE 发展的患者（n=14）以及既没有 PE 也没有 HT 的患者（n=422）。我们根据 PE 危险因素将患者按匹配分为三组（每组 n=5）：（1）PE：无 HT 但有 PE 发展，（2）HT：慢性高血压但无 PE，（3）对照：无 PE 或 HT。我们在进行全基因组亚硫酸氢盐测序之前成功优化了 cfDNA 分离过程。cfDNA 甲基化变化分析表明，PE 和 HT 组存在共同的易感性，主要来自母体。对显著差异甲基化区域和注释基因的评估表明，子痫前期和高血压组在孕早期存在共同的心血管易感性。我们推测母体心血管系统在 HDP 中起着关键作用，这在孕早期就已经很明显。
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