SODIUM TRANSPORT--GENETICS AND HYPERTENSION

钠转运——遗传学和高血压

• 批准号: 2216620
• 负责人: STEPHEN T TURNER
• 金额: $ 52.34万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-04-01 至 1996-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2216620
• 关键词: acidity /alkalinity; alleles; atrial natriuretic peptide; blood pressure; cardiovascular disorder diagnosis; cardiovascular disorder epidemiology; case history; disease /disorder proneness /risk; erythrocyte membrane; familial hypertension; family genetics; fluorescence spectrometry; genotype; hemodynamics; human subject; hydrogen; insulin sensitivity /resistance; ion transport; lipid metabolism; lithium; membrane transport proteins; potassium; sodium; sodium potassium exchanging ATPase; sympathetic nervous system

Essential hypertension (EHYT) is a common chronic disease contributing to morbidity, morality, and cost of health care. This renewal application is a continuation of our work to understand the genetic basis of interindividual variation in risk of EHYT in the population at large using the Rochester Family Heart Study (RFHS). This resource involves 4053 members of 560 multigeneration pedigrees ascertained without regard to health status who have undergone a physical examination and provided blood for laboratory studies. This resource is being utilized to address three major questions: 1) Which intermediate biochemical, physiological, and anthropomorphic traits predict blood pressure (BP) and contribute to the pathogenesis of EHYT? 2) Does allelic variation in one or more genes have large effects on any of these intermediate traits? 3) Does information about allelic variation improve prediction of risk of EHYT beyond what is provided by measure of the intermediate traits? AIMS 1-4 of this application focus on the first question, AIM 5 on the second, and AIM 6 on the third. AIM 1 will use 120 RFHS pedigrees to determine whether the single genetic or environmental factor identified as having a large effect on erythrocyte (RBC) sodium-lithium countertransport (NA-Li CNT) has a large impact on RBC and/or lymphocyte sodium-hydrogen exchange activity. AIM 2 seeks to determine whether measures of renal hemodynamic non- modulation (on high salt diet), renal tubular sodium (Na+) reabsorption, insulin resistance, heightened sympathetic nervous system activity, or alterations in lipid metabolism explain the statistical association between elevated Na-Li CNT and development of EHYT in these pedigrees. AIM 3 will establish the extent to which measures of the 24-hour ambulatory BP profile can be explained by traits studied in AIM 1 and 2. AIM 4 will consider 800 unrelated members of 294 RFHS pedigrees to determine if RBC Na-K ATPase pump, sodium-potassium cotransport, intracellular Na+, or plasma levels of atrial natriuretic peptide contribute to prediction of EHYT. AIM 5 will use all 2049 participants of these pedigrees to establish whether one or more single genes have major effects on traits identified as predictors of EHYT in AIM 4. AIM 6 will estimate the relative contribution of genes identified in AIM 5 to the prediction of EHYT.

原发性高血压是一种常见的慢性疾病， 发病率、道德和医疗费用的影响。 此续订 应用程序是我们工作的延续，以了解遗传 EHYT风险的个体间变异基础 使用罗切斯特家族心脏研究（RFHS）。 这个资源 涉及560个多代家系的4053名成员 无论健康状况如何， 检查并提供血液用于实验室研究。 此资源 它被用来解决三个主要问题：1）中间 生物化学、生理学和拟人化特征预测血液 血压（BP），并有助于发病机制EHYT？2)并 一个或多个基因中的等位基因变异对任何 这些中间特征？3)关于等位基因变异的信息 改善EHYT风险预测， 中间特征？ 本申请的AIMS 1-4侧重于 第一个问题，第二个是AIM 5，第三个是AIM 6。 AIM 1将使用120个RFHS谱系来确定单个 遗传或环境因素被确定为对 红细胞（RBC）钠-锂反向转运（NA-Li CNT）具有 对RBC和/或淋巴细胞钠-氢交换活性有很大影响。 目的2旨在确定肾血流动力学指标是否为非 调节（高盐饮食），肾小管钠（Na+）重吸收， 胰岛素抵抗，交感神经系统活动增强，或 脂质代谢的改变解释了 在这些家系中升高的Na-Li CNT和EHYT的发展之间。 AIM 3将确定24小时测量的范围 动态血压曲线可以用AIM 1和2中研究的特征来解释。 AIM 4将考虑294个RFHS家系的800个无关成员， 确定红细胞Na-K ATP酶泵，钠-钾共转运， 细胞内Na+或血浆心钠素水平 有助于EHYT的预测。 AIM 5将使用所有2049名参与者 以确定一个或多个单基因是否具有 在AIM 4中被确定为EHYT预测因子的性状的主要影响。 目的 6将估计AIM 5中鉴定的基因的相对贡献 对EHYT的预测。