Epigenomic Dysregulation in Preeclampsia-Associated Chronic Hypertension
Condition: Preeclampsia; Hypertension; Pregnancy Induced Hypertension
MeSH terms: Pre-Eclampsia; Hypertension, Pregnancy-Induced; Hypertension
Study type: Observational

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
    

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.
    

Observational model: Case-Control
Time perspective: Prospective
Sampling method: Probability Sample
Study population: 
        Females diagnosed with chronic hypertension with a prior pregnancy
      
Biospecimen description: 
      Sputum and peripheral blood will be collected for DNA extraction and epigenetic analyses.
    
Keywords: preeclampsia; hypertension; blood pressure; pregnancy induced hypertension; chronic hypertension