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Sample Preparation to Bioinformatics Analysis of DNA Methylation: Association Strategy for Obesity and Related Trait Studies
Published on: May 6, 2022
Hypertensive disorders of pregnancy share common cfDNA methylation profiles
Marialuigia Spinelli1, Jarmila A Zdanowicz1, Irene Keller2
1Department of Obstetrics and Gynecology, Department of Biomedical Research, University Hospital, Inselspital, University of Bern, Friedbuehlstrasse 19, 3010, Bern, Switzerland.
Insights
Early pregnancy epigenetic changes in cell-free DNA (cfDNA) reveal a shared maternal cardiovascular predisposition in hypertensive disorders of pregnancy (HDP) and chronic hypertension. This suggests the maternal cardiovascular system
Area of Science:
- Obstetrics and Gynecology
- Genetics and Epigenetics
- Cardiovascular Health
Background:
- Hypertensive disorders of pregnancy (HDP) are a major cause of perinatal complications.
- Epigenetic alterations are implicated in the cardio-metabolic dysregulation underlying HDP.
- Early pregnancy epigenetic changes in cell-free DNA (cfDNA) for HDP remain understudied.
Purpose of the Study:
- To investigate cfDNA methylation profiles in early pregnancy (11-14 weeks gestation) in women who develop preeclampsia (PE) or have chronic hypertension (HT).
- To identify epigenetic signatures associated with HDP and explore their maternal origin.
Main Methods:
- Analysis of cfDNA methylation profiles using whole genome bisulfite sequencing.
- Comparison of methylation patterns in three matched groups: PE development, chronic HT, and controls.
- Optimization of cfDNA isolation for accurate sequencing.
Main Results:
- cfDNA methylation analysis revealed a common predisposition in both PE and HT groups, primarily of maternal origin.
- Significant differentially methylated regions and annotated genes indicated a shared cardiovascular predisposition in the first trimester for PE and HT.
- These findings were evident as early as 11-14 weeks of gestation.
Conclusions:
- The maternal cardiovascular system plays a pivotal role in the development of HDP.
- Epigenetic changes in cfDNA during the first trimester can indicate an increased risk for HDP.
- Early detection of cardiovascular predisposition through cfDNA methylation may inform future preventative strategies for HDP.
Abstract:
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.
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