DNA Methylation of Endoglin Pathway Genes in Pregnant Women With and Without Preeclampsia

Allison H Rietze; Yvette P Conley; Dianxu Ren; Cindy M Anderson; James M Roberts; Arun Jeyabalan; Carl A Hubel; Mandy J Schmella

doi:10.1177/2516865720959682

DNA Methylation of Endoglin Pathway Genes in Pregnant Women With and Without Preeclampsia

Epigenet Insights. 2020 Oct 9:13:2516865720959682. doi: 10.1177/2516865720959682. eCollection 2020.

Authors

Allison H Rietze¹, Yvette P Conley^{1

2}, Dianxu Ren³, Cindy M Anderson⁴, James M Roberts^{5

6

7

8}, Arun Jeyabalan^{5

6

8}, Carl A Hubel^{5

6}, Mandy J Schmella¹

Affiliations

¹ Department of Health Promotion and Development (School of Nursing), University of Pittsburgh, Pittsburgh, PA, USA.
² Department of Human Genetics (Graduate School of Public Health), University of Pittsburgh, Pittsburgh, PA, USA.
³ Department of Health and Community Systems (School of Nursing), University of Pittsburgh, Pittsburgh, PA, USA.
⁴ Martha S Pitzer Center for Women, Children, and Youth (College of Nursing), The Ohio State University, Columbus, OH, USA.
⁵ Department of Obstetrics, Gynecology, & Reproductive Sciences (School of Medicine), University of Pittsburgh, PA, USA.
⁶ Magee-Womens Research Institute, Pittsburgh, PA, USA.
⁷ Department of Epidemiology (Graduate School of Public Health), University of Pittsburgh, Pittsburgh, PA, USA.
⁸ Clinical and Translational Science Institute, University of Pittsburgh, Pittsburgh, PA, USA.

Abstract

Objective: We compared blood-based DNA methylation levels of endoglin (ENG) and transforming growth factor beta receptor 2 (TGFβR2) gene promoter regions between women with clinically-overt preeclampsia and women with uncomplicated, normotensive pregnancies.

Methods: We used EpiTect Methyl II PCR Assays to evaluate DNA methylation of CpG islands located in promoter regions of ENG (CpG Island 114642) and TGFβR2 (CpG Island 110111). Preeclampsia was diagnosed based on blood pressure, protein, and uric acid criteria. N = 21 nulliparous preeclampsia case participants were 1:1 frequency matched to N = 21 nulliparous normotensive control participants on gestational age at sample collection (±2 weeks), smoking status, and labor status at sample collection. Methylation values were compared between case and control participant groups [(ENG subset: n = 20 (9 cases, 11 controls); TGFβR2 subset: n = 28 (15 cases, 13 controls)].

Results: The majority of the preeclampsia cases delivered at ⩾34 weeks' gestation (83%). Average methylation levels for ENG ([M ± (SD)]; Case Participant Group = 6.54% ± 4.57 versus Control Participant group = 4.81% ± 5.08; P = .102) and TGFβR2 (Case Participant Group = 1.50% ± 1.37 vs Control Participant Group = 1.70% ± 1.40; P = .695) promoter CpG islands did not differ significantly between the participant groups. Removal of 2 extreme outliers in the ENG analytic subset revealed a trend between levels of ENG methylation and pregnancy outcome (Case Participant Group = 5.17% ± 2.16 vs Control Participant Group = 3.36% ± 1.73; P = .062).

Conclusion: Additional epigenetic studies that include larger sample sizes, investigate preeclampsia subtypes, and capture methylation status of CpG island shores and shelves are needed to further inform us of the potential role that ENG and TGFβR2 DNA methylation plays in preeclampsia pathophysiology.

Keywords: Methylation; pre-eclampsia; pregnancy.

Abstract

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