HYPERGEN--GENETICS OF LEFT VENTRICULAR HYPERTROPHY

HYPERGEN--左心室肥大的遗传学

• 批准号: 6043887
• 负责人: Donna K Arnett
• 金额: $ 37.91万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-08-10 至 2000-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6043887
• 关键词: cardiovascular disorder epidemiology; clinical research; disease /disorder proneness /risk; echocardiography; gene environment interaction; genetic markers; human genetic material tag; human population genetics; human subject; insulin; linkage mapping; obesity; quantitative trait loci; stressor; ventricular hypertrophy

DESCRIPTION: (Adapted from the Investigator's Abstract) Studies of left ventricular (LV) hypertrophy detected by echocardiography demonstrate its importance in cardiovascular morbidity and mortality, independent of blood pressure and other cardiovascular risk factors. The goal of this project is to evaluate the genetic determinants of LV hypertrophy. Building upon HyperGEN (a network established to investigate the genetic determinants of hypertension as part of the NHLBI Genetic Determinants of High Blood Pressure RFA (#6-94-011), this application proposes to perform a targeted echocardiographic examination on 2,575 HyperGEN participants in four field centers as part of the HyperGEN clinical examination. The HyperGEN study is designed to identify the genetic determinants of hypertension by selecting severely and mildly affected hypertensives from existing epidemiologic populations, affected siblings of these probands, a random sample of individuals from the cohorts, and normotensive relatives of the probands. These individuals will be examined over a three year period, beginning in August, 1996. There are five specific aims for this echocardiography project. First, the investigators will characterize LV structure and function in 2,575 individuals. Second, they will define LV structural phenotypes based on four geometric patterns(normal geometry, concentric remodeling, concentric LV hypertrophy, and eccentric LV hypertrophy). Third, they will examine a highly select group of candidate genes and their association with LV mass (measured as a quantitative trait to increase statistical power) and geometric patterns. Fourth, using quantitative trait loci analyses, the investigators will test for linkage of 240 anonymous, evenly spaced genetic markers with LV mass and geometric patterns. The fifth aim is to evaluate interactions between genes and potential risk factors for LV hypertrophy (insulin, glucose, blood pressure response to mental and physical stressors, dietary and urinary electrolytes, obesity) and LV mass and geometry. The proposed project has the advantages of (i) incorporation into an already funded study designed to examine. the genetic determinants of hypertension (more than 500,000 individual genotypes are measured as part of HyperGEN); (ii) recruitment of participants from on-going population-based studies of well-characterized cohorts; (iii) collaboration with experienced investigators in research echocardiography, an experienced echocardiography reading center (under the direction of Dr. Richard Devereux), statistical expertise in association and linkage analyses (directed by Dr. D. C. Rao), and genetic testing by a state-of-the-art laboratory(directed by Dr. Lalouel). It will, therefore, be an important and cost-effective contribution to the knowledge and understanding about the genetics of LV hypertrophy.

描述：(改编自《调查者摘要》)左派研究 超声心动图检测到的左心室肥厚表明 与血液无关的心血管发病率和死亡率的重要性 压力和其他心血管危险因素。这个项目的目标是 目的探讨左心室肥厚的遗传决定因素。建立在 HyperGEN(一个为研究糖尿病的遗传决定因素而建立的网络 高血压是高血压病的NHLBI基因决定因素之一 压力RFA(#6-94-011)，此应用程序建议执行有针对性的 2575名HyperGEN受试者四个领域的超声心动图检查 作为HyperGEN临床检查的一部分。 HyperGEN研究旨在确定糖尿病患者的遗传决定因素 从高血压患者中选择影响严重和轻微的高血压患者 现有的流行病学人群，这些先证者的受影响兄弟姐妹，a 队列中随机抽样的个体和血压正常的亲属 先驱们。这些人将在三年内接受检查， 从1996年8月开始。 这个超声心动图项目有五个具体目标。首先， 研究人员将在2575名患者中表征左心室的结构和功能 个人。其次，他们将根据以下条件定义LV结构表型 四种几何模式(正常几何、同心重塑、同心 左室肥厚和偏心性左室肥厚)。第三，他们将审查一项 高选择候选基因组及其与左心室重量的关系 (以数量性状衡量，以增加统计能力)和 几何图案。第四，利用数量性状基因座分析， 研究人员将测试240个匿名、均匀分布的基因的连锁 具有LV质量和几何图案的标记。第五个目标是评估 基因与左心室肥厚潜在危险因素的相互作用 (胰岛素、葡萄糖、血压对精神和身体压力的反应， 饮食和尿液电解质、肥胖)以及左心室重量和几何构型。 拟议的项目具有以下优点：(I)并入已有的 受资助的研究旨在检查。高血压的遗传决定因素 (作为HyperGEN的一部分，测量了500,000多个个体基因类型)； (2)从正在进行的基于人口的研究中征聘参与者 特点良好的队列；(3)与有经验的人合作 研究人员在研究超声心动图，一种有经验的超声心动图 阅读中心(理查德·德弗罗博士指导)，统计 在关联和连锁分析方面的专业知识(由D.C.Rao博士指导)， 由最先进的实验室进行基因检测(由Dr。 Lalouel)。因此，这将是一项重要和具有成本效益的 对LV遗传学知识和理解的贡献 肥大。