Genomics of Endoglin Pathway in Preeclampsia (GEPP)

描述（由申请人提供）：先兆子痫（PE）是一种多方面的妊娠疾病，在全球范围内显著导致孕产妇和胎儿的发病率和死亡率。虽然有缺陷的滋养层细胞入侵，失败的重构母体血管灌注胎盘，和母体综合征（高血压，蛋白尿等）与PE的过程已被很好地记录，负责这些过程的潜在病理生理机制仍然是难以捉摸的，唯一的治愈性治疗仍然是迅速交付。然而，最近的研究集中在内皮糖蛋白的潜在参与上，内皮糖蛋白是转化生长因子β家族的膜结合蛋白受体，其密切参与滋养层侵袭和血管壁稳态的调节。尽管研究似乎已经量化了先兆子痫妇女血清中可溶性内皮糖蛋白浓度的显著升高，但研究尚未集中在分子水平上对内皮糖蛋白途径的研究上，这有可能解释PE易感性的变化。因此，由于PE相关研究中的这一差距，并且由于国立护理研究所强调通过鉴定高危个体的易感基因来促进健康和预防疾病，因此提出的途径特异性、候选基因、病例对照研究旨在：1.）研究参与内皮联蛋白途径的母体基因的变异对PE发展的影响; 2.）探索参与内皮糖蛋白途径的母体/胎儿二分体基因的变异对PE发展的影响。所提出的方法包括利用i-PLEX Gold SNP Assay进行基因型收集和利用R Genetics Package的HAPLO.STATS软件包（版本1.2.2）和Haploview（版本3.32）进行单倍型分配。这项研究的结果将有望为我们了解子痫前期发生的潜在病理生理机制提供信息。此外，由于PE使所有妊娠的3-5%复杂化，并且对母亲和胎儿的显著的短期和长期健康后果负责，这可能消耗大量的医疗保健费用，因此对PE病理生理学的全面了解对于旨在预防、检测和治疗先兆子痫的干预措施的设计和实施将是非常宝贵的。通过这些干预措施，人们希望改善健康状况，减少与体育有关的医疗保健费用的消费。

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.