Preeclampsia (PE) represents a multi-faceted disorder of pregnancy that significantly contributes to maternal and fetal morbidity and mortality worldwide. Although the processes of defective trophoblast invasion, failed remodeling of the maternal vessels perfusing the placenta, and the maternal syndrome (hypertension, proteinuria, etc) associated with PE have been well documented, the underlying pathophysiologic mechanisms responsible for these processes continue to remain elusive and the only curative treatment remains prompt delivery. However, recent research has focused on the potential involvement of endoglin, which is a membrane-bound protein receptor of the transforming growth factor beta family intimately involved in regulation of trophoblast invasion and vessel wall homeostasis. Although research appears to have quantified the significantly elevated concentrations of soluble endoglin present in the sera of preeclamptic women, research has yet to focus on the investigation of the endoglin pathway at the molecular level, which has the potential to explain the variability in susceptibility to PE. Thus, as a result of this gap in PE related research and because of the National Institute of Nursing Research's emphasis on promotion of health and prevention of disease through the identification of susceptibility genes for at-risk individuals, the proposed pathway specific, candidate gene, case-control research study seeks to: 1.) investigate variation in maternal genes involved in the endoglin pathway for impact on development of PE;2.) explore variation in maternal/fetal dyad genes involved in the endoglin pathway for impact on development of PE. Proposed methods include the utilization of i-PLEX Gold SNP Assay for genotype collection and the HAPLO.STATS package (version 1.2.2) of the R Genetics Package and Haploview (version 3.32) for haplotype assignment. Findings from this proposed study will hopefully inform our knowledge of the underlying pathophysiologic mechanisms involved in preeclampsia development. Furthermore, because PE complicates 3-5% of all pregnancies and is responsible for significant short and long term health consequences of the mother and fetus that can consume large amounts of healthcare dollars, a comprehensive understanding of PE pathophysiology will be invaluable to the design and implementation of interventions aimed at prevention, detection, and treatment of preeclampsia. Through such interventions, it is the hope that improved health outcomes and decreased consumption of healthcare dollars related to PE will result.
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