Genomics of Endoglin Pathway in Preeclampsia (GEPP)

先兆子痫内皮糖蛋白通路基因组学 (GEPP)

• 批准号: 7980164
• 负责人: Mandy Jo Schmella
• 金额: $ 4.14万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-01 至 2012-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7980164
• 关键词: Binding; Binding Proteins; Biological Assay; Candidate Disease Gene; Case-Control Studies; Cell Membrane Permeability; Collection; Consumption; Detection; Development; ENG gene; Endoglin; Family; Fetus; Functional disorder; Genes; Genetic; Genetic Variation; Genomics; Genotype; Gold; Haplotypes; Health; Health Promotion; Healthcare; Homeostasis; Hypertension; Individual; Intervention; Investigation; Knowledge; Membrane; Methods; Molecular; Morbidity - disease rate; Mothers; National Institute of Nursing Research; Outcome; Pathogenesis; Pathway interactions; Placenta; Play; Pre-Eclampsia; Predisposition; Pregnancy; Prevention; Process; Proteins; Proteinuria; Regulation; Research; Risk; Role; Serum; Susceptibility Gene; Syndrome; System; Techniques; Transforming Growth Factor beta Receptors; Variant; Vasodilation; Woman; case control; design; disorder prevention; fetal; improved; insight; mortality; normotensive; pregnancy disorder; research study; trophoblast

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.

描述(由申请人提供)：先兆子痫(PE)是一种多方面的妊娠障碍，在世界范围内对孕产妇和胎儿的发病率和死亡率有重要影响。虽然有缺陷的滋养细胞侵入，母体胎盘血管重构失败，以及与PE相关的母体综合征(高血压、蛋白尿等)的过程已经被很好地记录下来，但导致这些过程的潜在病理生理机制仍然是难以捉摸的，唯一的治愈方法仍然是及时分娩。然而，最近的研究集中在endoglin的潜在参与，它是转化生长因子β家族的一种膜结合蛋白受体，密切参与调节滋养层细胞的侵袭和管壁稳态。尽管研究似乎已经量化了先兆子痫妇女血清中显著升高的可溶性endoglin浓度，但研究尚未集中在分子水平上的endoglin途径的研究，这有可能解释PE易感性的差异。因此，由于体育相关研究的这一空白，以及由于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，拟议的特定途径、候选基因、病例对照研究试图：1.研究Enoglin途径中母体基因的变异对PE发育的影响；探索与Enoglin通路有关的母婴二联体基因变异对PE发生的影响。建议的方法包括利用I-PLEX Gold SNP分析进行基因型收集，以及利用R Genetics程序包的HAPLO.STATS程序包(版本1.2.2)和单倍体视图(版本3.32)进行单倍型分配。这项拟议的研究结果有望为我们提供有关先兆子痫发生的潜在病理生理机制的信息。此外，由于PE导致3%-5%的妊娠并发症，并对母亲和胎儿的重大短期和长期健康后果负责，这可能会消耗大量的医疗费用，因此对PE病理生理学的全面了解对于设计和实施旨在预防、检测和治疗先兆子痫的干预措施将是非常宝贵的。通过这样的干预，人们希望改善健康结果，减少与PE相关的医疗费用的消耗。