GENETIC POLYMORPHISMS AND PRE-ECLAMPSIA

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者的研究机构。 大约6%的妊娠并发高血压和蛋白尿，通常称为先兆子痫。先兆子痫/子痫（P/E）是孕产妇和新生儿发病率和死亡率的危险因素。虽然已经确定了一些风险因素，但P/E的根本原因仍然未知。 P/E在处于不利社会经济地位的妇女中更为常见，发生率高达30%。在这个美洲印第安人（AI）社区中，P/E的发生率尚不清楚，但数据显示至少为5.4%。 在非印度人中进行的研究表明，P/E的风险与影响凝血级联反应的遗传变化（凝血因子V Leiden）、纤溶酶原激活抑制剂-1（派-1）异常、脂质异常（脂蛋白脂肪酶）和肾脏生理学（盐皮质激素受体和肾素基因）有关。派-1基因与胰岛素抵抗（常见于AI人群）相关，适合二甲双胍治疗，因此具有额外的重要性。 这项建议将在专门的印迹纸上收集大约100个病例和200个匹配的对照组的DNA样本。将使用PCR扩增、限制性内切酶消化和电泳凝胶上的产物分析对可能具有功能意义的遗传多态性进行基因分型。将检查该人群中风险基因型与P/E的可能关联。将从产前诊所招募大约560名额外的参与者进行前瞻性分析。 关于这些遗传多态性的患病率及其与P/E的可能相关性的信息是不可用的，并且不仅有助于更好地理解P/E的潜在病理生理学，而且还有助于公共卫生和临床使用，以判断遗传筛查测试在该特定人群中的效用，也许其他相关的AI社区。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. About 6% of pregnancies are complicated by hypertension and proteinuria, commonly termed preeclampsia. Preeclampsia/eclampsia (P/E) is a risk factor for both maternal and neonatal morbidity and mortality. Although some risk factors have been identified, the underlying cause of P/E remains unknown. P/E is more common among women in disadvantaged socio-economic populations, with incidences of up to 30%. The incidence of P/E in this American Indian (AI) community is unknown, but data suggests that it is at least 5.4%. Research in non-Indian populations has related the risk of P/E to genetic changes influencing the blood clotting cascade (factor V Leiden), abnormalities of plasminogen activating inhibitor-1 (PAI-1)), lipid abnormalities (lipoprotein lipase) and renal physiology (mineralocorticoid receptor and renin genes). The PAI-1 gene is associated with insulin resistance (common in AI populations), amenable to treatment with metformin, and thus of additional importance. This proposal will collect DNA samples on specialized blotting paper, from about 100 cases and 200 matched controls. Genetic polymorphisms of possible functional significance will be genotyped using PCR amplification, restriction endonuclease digestion and analysis of products on electrophoresis gels. The possible association of risk genotypes in this population to P/E will be examined. Approximately 560 additional participants will be enrolled from prenatal clinics for a prospective analysis. Information about the prevalence of these genetic polymorphisms and their possible relevance to P/E is not otherwise available and is useful not only to better understand the underlying pathophysiology of P/E; but also for public health and clinical use in judging the utility of genetic screening tests in this particular population and perhaps other related AI communities.