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DNA Methylation Patterns Suggest Future and Heritable Cardiovascular Risk: Potential for Transformation of Cardiovascular Screening in Preeclampsia


DNA Methylation Patterns Suggest Future and Heritable Cardiovascular Risk: Potential for Transformation of Cardiovascular Screening in Preeclampsia

Background: §Cardiovascular disease is the leading cause of death among women in the U.S. §Women with preeclampsia and their children have a significantly higher risk for future cardiovascular disease.  §Heritable risk of complex, non-Mendelian conditions may be the result of epigenomic dysregulation. §Preliminary data from our laboratory in maternal while blood cells and placental tissue of fetal origin indicate unique patterns of DNA methylation developed during pregnancy complicated by preeclampsia. §Alterations in DNA methylation passed from mother to child represent a potential mechanism for cardiovascular risk and biomarkers for cardiovascular risk screening. §Our central hypothesis is that distinct epigenetic patterns of DNA methylation in preeclampsia are associated with future and heritable risk for cardiovascular disease.   Purpose: §The purpose of this study was to identify the functional implications of differential DNA methylation patterns in women with preeclampsia and to determine the potential association with cardiovascular disease. §It was anticipated that identification of differentially methylated genes involved in the regulation of cardiovascular function would provide mechanistic insight and screening biomarkers for cardiovascular disease.   Methods: •Prospective collection of maternal peripheral blood from nulliparous women in early pregnancy •Placental chorionic tissue collection at delivery •Comparison of genome-wide DNA methylation patterns in women with preeclampsia and normotensive pregnancy outcomes (n=6/group) •Quantification of DNA methylation using Illumina Infinium® bead array •Delta-beta criteria > 0.2 or < -0.2 to determine significant change in methylation status •Group differences in mean DNA methylation analyzed by t-test •Significance determined at p<0.05 •Identification of functional association of differentially methylated genes with cardiovascular disease •Database for Annotation, Visualization and Integrated Discovery (DAVID) Bioinformatics Resources 6.7 •Significance of gene-term enrichment was determined by a modified Fisher’s exact test (EASE score of p<0.05), indicating that clusters are significantly more enriched than by random chance.   Conclusions: §Epigenomic marks  in DNA  methylation common to maternal and placental tissue of fetal origin during acute preeclampsia provides a screening target for future and heritable risk of cardiovascular disease.   §Functional classification of differentially methylated genes allows for the exploration of larger biological networks and a comprehensive understanding regarding the association of genes with each other and with functional outcomes of cardiovascular disease.

§Identification of functional clusters reveals mechanistic insights that can be used for prevention and to develop targeted treatment of cardiovascular disease as a consequence of preeclampsia.

Acknowledgements:

§Funding for this project provided by the Robert Wood Johnson Nurse Faculty Scholar Award (CMA, 64202)    
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