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Blood-based DNA methylation levels of endoglin pathway genes: do they differ in women with and without clinically-overt preeclampsia?

Rietze, Allison (2018) Blood-based DNA methylation levels of endoglin pathway genes: do they differ in women with and without clinically-overt preeclampsia? Undergraduate Thesis, University of Pittsburgh. (Unpublished)

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Abstract

This observational pilot study was designed to test the hypothesis that blood-based DNA methylation levels of endoglin (ENG) and transforming growth factor beta receptor 2 (TGFβR2) gene promoter regions differ significantly when comparing women with clinically-overt preeclampsia to normotensive pregnant women matched on key variables. A 1:1 frequency matched case-control candidate gene design was used to evaluate ENG and TGFβR2 gene promoter methylation levels. Methylation data were collected using the EpiTect Methyl II quantitative Polymerase Chain Reaction (PCR) Assay (Qiagen® Inc., Germantown, Maryland). The promoter region CpG islands evaluated included ENG (CpG Island 114642) and TGFβR2 (CpG Island 110111). Genomic DNA was extracted from maternal peripheral white blood cells via protein precipitation. The sample included n=22 preeclampsia cases 1:1 frequency matched to n=22 normotensive controls on gestational age at sample collection (± 2 weeks), smoking status, and labor status at sample collection. All participants were Caucasian and nulliparous. Preeclampsia was diagnosed based on blood pressure, protein, and uric acid criteria. Parametric and nonparametric analyses were utilized to compare demographic and clinical characteristics between cases and controls. A non-parametric approach (Mann-Whitney U) was utilized to compare methylation levels for both candidate genes between cases and controls. Average methylation levels for both ENG (Cases [M±(SD)]= 6.54% ± 4.57; Controls= 4.81% ± 5.08; p=0.102) and TGFβR2 (Cases= 1.5% ± 1.37; Controls= 1.7% ± 1.4; p= 0.695) promoter CpG islands did not significantly differ between cases and controls. The role that the ENG pathway plays in preeclampsia pathogenesis is not fully understood. Evaluation of ENG pathway blood-based DNA methylation levels will better inform us of the potential role that ENG and TGFβR2 DNA methylation plays in preeclampsia pathophysiology, including the maternal response to placental dysfunction. Although this study did not reveal detectable differences in blood-based DNA methylation levels of ENG and TGFβR2 gene promoters during clinically-overt preeclampsia, additional epigenetic studies with larger sample sizes are needed to enhance our understanding of preeclampsia pathophysiology and to inform the development of prevention, detection (e.g. biomarkers), and treatment modalities that improve maternal and fetal health outcomes.


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Details

Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Rietze, Allisonahr22@pitt.eduahr22
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairSchmella, Mandymjb111@pitt.edu
Committee MemberConley, Yvetteyconley@pitt.edu
Committee MemberRen, Dianxudir8@pitt.edu
Committee MemberAnderson, Cindyanderson.2765@osu.edu
Date: 25 April 2018
Date Type: Publication
Defense Date: 4 April 2018
Approval Date: 25 April 2018
Submission Date: 19 April 2018
Access Restriction: 1 year -- Restrict access to University of Pittsburgh for a period of 1 year.
Number of Pages: 34
Institution: University of Pittsburgh
Schools and Programs: School of Nursing > Nursing
University Honors College
Degree: BSN - Bachelor of Science in Nursing
Thesis Type: Undergraduate Thesis
Refereed: Yes
Uncontrolled Keywords: methylation, hypertension in pregnancy, endoglin, biomarker
Date Deposited: 25 Apr 2018 17:24
Last Modified: 25 Apr 2019 05:15
URI: http://d-scholarship.pitt.edu/id/eprint/34340

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