GENETIC DETERMINANTS OF HIGH BLOOD PRESSURE

高血压的遗传决定因素

• 批准号: 2232876
• 负责人: ALAN B WEDER
• 金额: $ 33.19万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-09-05 至 2000-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2232876
• 关键词: GENETIC; DETERMINANTS; BLOOD; PRESSURE

In this proposal, we will employ several synergistic strategies to identify novel genetic determinants of hypertension. Our primary strategy will be to use genomic markers (both anonymous markers and candidate genes) spanning the human genome at an average density of 10 cM to examine 250 white sibships in Tecumseh, MI for genetic linkage with blood pressure and the intermediate phenotypic features of elevated erythrocyte lithium- sodium countertransport, the hyperkinetic hyperadrenergic state, decreased proximal tubular lithium clearance (a measure of proximal tubular sodium handling), and elements of the renin-angiotensin system (plasma renin and angiotensin-converting enzyme activity and serum angiotensinogen concentration). Positive findings will be confirmed by further testing for linkage in a population of 250 African-American sibships in Maywood, IL. In addition, we will seek to develop new candidate genes for hypertension by identifying genes linked to the hypertensive phenotype in segregating rat populations derived from inbred normotensive and hypertensive strains; homologues of genes identified in rats will be searched for in humans. Having developed and refined important candidates in our sibships and rat models, we will test associations in several extant black populations in Jamaica and Nigeria as well as in subjects in Tecumseh and Maywood selected from the extremes of the populational blood pressure distribution. To carry out these investigations, we have brought together well- characterized population resources suitable for the identification of probands and families affected by hypertension (Tecumseh, MI and Maywood, IL), two experienced teams of epidemiological investigators at the University of Michigan and Loyola University of Chicago, state-of-the-art genotyping facilities run by experienced investigators at Case Western Reserve University, a superb team of statistical geneticists, an animal resource with a proven record of productivity in identifying genetic loci regulating blood pressure in hypertensive rats, and several relevant population resources suitable for case-control studies (Nigeria, Jamaica). We are confident that these resources will permit us to accomplish our primary aim of identifying genetic determinants of hypertension.

在此提案中，我们将采用几种协同策略来 确定高血压的新型遗传决定因素。我们的主要策略 将使用基因组标记（匿名标记和候选者 基因）跨越人类基因组的平均密度为10 cm 密歇根州Tecumseh的250个白人sibships与血压遗传联系 以及升高的红细胞锂的中间表型特征 钠反肾上腺肾上腺素能状态钠降低 近端管状锂清除率（近端管状钠的量度 处理）和肾素 - 血管紧张素系统的元素（血浆肾素和 血管紧张素转化酶活性和血管激素原 专注）。积极的发现将通过进一步测试来确认 伊利诺伊州梅伍德市250名非裔美国人的人口的联系。 此外，我们将寻求为高血压开发新的候选基因 通过识别与高血压表型相关的基因 大鼠种群源自近交性和高血压菌株； 将在人类中搜索大鼠鉴定的基因的同源物。 在我们的小伙子和老鼠中开发和完善了重要的候选人 模型，我们将在几个现有的黑人种群中测试关联 牙买加和尼日利亚以及Tecumseh和Maywood的主题 从人口血压的极端选择 分配。 为了进行这些调查，我们将 特征的人口资源适合识别 受到高血压影响（Tecumseh，Mi和Maywood， il），两个经验丰富的流行病学研究人员团队 密歇根大学和芝加哥洛约拉大学，最先进的 Case Western经验丰富的调查员经营的基因分型设施 储备大学，一支精湛的统计遗传学家团队，动物 在识别遗传基因座的生产力的可靠记录的资源 调节高血压大鼠的血压和几个相关 适合病例对照研究的人口资源（牙买加尼日利亚）。 我们相信这些资源将使我们能够完成我们的 鉴定高血压的遗传决定因素的主要目的。