Epigenomic Dysregulation in Preeclampsia-Associated Chronic Hypertension

Sponsor

Ohio State University (Other)

Overall Status

Completed

CT.gov ID

NCT01682304

Collaborator

(none)

Enrollment

Location

Duration (Months)

0.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Preliminary data from the investigator's lab identified novel patterns of differential DNA methylation in genes regulating cardiovascular and metabolic function in blood from women during the first trimester of pregnancy who were destined to develop preeclampsia (PE) in the third trimester. Further, common patterns of differential DNA methylation were found in the common genes from placental tissue at time of birth in the same women after diagnosis with PE, suggesting that the epigenomic patterns that predict pregnancy-induced hypertension may also underlie the development of chronic hypertension years after.

It is unknown whether aberrant DNA methylation in pregnancy-induced hypertension is the mechanism by which chronic hypertension develops in these women remote from pregnancy nor is it known if hypertension remote from PE is as responsive to therapeutic treatment of hypertension compared to women who develop hypertension without history of PE. The investigators plan to objectively test the central hypothesis and attain the objective of this project

Condition or Disease	Intervention/Treatment	Phase
Preeclampsia Hypertension Pregnancy Induced Hypertension

Detailed Description

Women comprise 51% of the total heart disease deaths in the United States (NC with an estimated economic cost expected to climb to more than $258 billion. Hypertension, a prevalent manifestation of early cardiovascular disease, is a silent condition that contributes to significant adverse health consequences. Preeclampsia (PE), a form of pregnancy-induced hypertension diagnosed in the second half of pregnancy, is now established as a non-modifiable risk factor for future development of hypertension. As PE carries a familial risk for future development of PE in female offspring, the implications of increased risk for PE-associated future development of chronic hypertension further compounds the significance of this unique cardiovascular risk. This raises an important health concern, though little is known about the mechanisms underlying risk of PE-associated future chronic hypertension. As epigenetic patterns of DNA methylation are associated with transfer across generations and are known to be dysregulated in PE, we propose to test the central hypothesis that differential DNA methylation patterns in key cardiovascular genes identified in women with PE serve as a biomarker and predictor for therapeutic responsiveness for the remote diagnosis and prognosis of chronic hypertension, respectively. Therefore, the purpose of this study is to identify distinct epigenetic patterns of DNA methylation associated with preeclampsia (PE) that underlie the future development of hypertension and to determine the implication on responses to moderators and therapeutic interventions in the management of chronic hypertension.Univariate analysis of variance will be used to test associations between DNA methylation in genes and chronic hypertension among women with and without a history of preeclampsia. We will use multiple linear regression to examine differences in treatment responses to high blood pressure based on DNA methylation patterns in candidate cardiovascular genes.

Study Design

Study Type:

Observational

Actual Enrollment :

12 participants

Observational Model:

Case-Control

Time Perspective:

Prospective

Official Title:

Observational Study of Epigenomic Dysregulation in Preeclampsia-Associated Chronic Hypertension

Study Start Date :

May 1, 2012

Actual Primary Completion Date :

Mar 1, 2014

Actual Study Completion Date :

Mar 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
History of Preeclampsia Chronic hypertension with history of preeclampsia Chronic hypertension without history of preeclampsia

Outcome Measures

Primary Outcome Measures

DNA methylation pattern [age 30-65]
Determine DNA methylatiion patterns in women with hypertension who have/have not had a prior diagnosis of preeclampsia

Secondary Outcome Measures

Vascular function [aged 30-65]
Determine differences in vascular function among women aged 30-65, diagnosed with hypertension and who have/have not had a prior diagnosis of preeclampsia