Genomics of Endoglin Pathway in Preeclampsia (GEPP)

描述（由申请人提供）：先兆子痫（PE）是一种多面性的妊娠疾病，在全球范围内对孕产妇和胎儿的发病率和死亡率有重要影响。尽管与PE相关的滋养细胞侵袭缺陷、灌注胎盘的母体血管重构失败以及母体综合征（高血压、蛋白尿等）的过程已经得到了很好的记载，但导致这些过程的潜在病理生理机制仍然是难以捉摸的，唯一的治疗方法仍然是及时分娩。然而，最近的研究集中在内啡肽的潜在参与上，内啡肽是转化生长因子β家族的一种膜结合蛋白受体，密切参与滋养细胞侵袭和血管壁稳态的调节。虽然研究似乎已经量化了子痫前期妇女血清中可溶性内啡肽浓度的显著升高，但研究尚未集中在分子水平上对内啡肽途径的研究，这有可能解释PE易感性的变异性。因此，由于PE相关研究的空白，以及国家护理研究所强调通过识别高危个体的易感基因来促进健康和预防疾病，提出的途径特异性，候选基因，病例对照研究旨在：1)调查参与内啡肽途径的母体基因变异对PE发展的影响；2)探讨参与内啡肽通路的母/胎双染色体基因变异对PE发展的影响。提出的方法包括利用i-PLEX金SNP法收集基因型和HAPLO。R Genetics package的STATS包（版本1.2.2）和Haploview（版本3.32）用于单倍型分配。本研究的发现将有助于我们了解子痫前期发展的潜在病理生理机制。此外，由于PE并发症占所有妊娠的3-5%，并且对母亲和胎儿的短期和长期健康后果负责，可以消耗大量的医疗保健费用，因此全面了解PE病理生理学对于设计和实施旨在预防、检测和治疗子痫前期的干预措施将是非常宝贵的。通过这些干预措施，希望能够改善健康结果，减少与体育相关的医疗保健费用的消耗。

DESCRIPTION (provided by applicant): 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.