HYPERGEN--GENETICS OF LEFT VENTRICULAR HYPERTROPHY

HYPERGEN--左心室肥大的遗传学

• 批准号: 2750535
• 负责人: Donna K Arnett
• 金额: $ 43.3万
• 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/2750535
• 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：（改编自研究者摘要）左 超声心动图检测到的心室（LV）肥大表明其 在心血管发病率和死亡率中的重要性，与血液无关 压力和其他心血管风险因素。 这个项目的目标是 评估左心室肥大的遗传决定因素。 基础上 HyperGEN（一个网络，建立调查的遗传决定因素， 高血压作为NHLBI高血压遗传决定因素的一部分 压力RFA（#6-94-011），本申请建议进行靶向 在四个领域对2，575名HyperGEN参与者进行超声心动图检查 作为HyperGEN临床检查的一部分。 HyperGEN研究旨在确定以下遗传决定因素： 高血压，选择严重和轻度影响的高血压患者， 现有的流行病学人群，这些先证者的受影响兄弟姐妹， 从队列中随机抽取个体，和血压正常的亲属， 先证者 这些人将在三年内接受审查， 从1996年8月开始。 本超声心动图项目有五个具体目标。 一是 研究人员将在2575例患者中描述LV结构和功能 个体 其次，他们将根据以下因素定义LV结构表型： 四种几何图案（正常几何形状、同心重塑、同心 LV肥大和离心性LV肥大）。 第三，他们将研究一个 高度选择候选基因组及其与LV质量的关联 （作为一种数量性状来衡量，以增加统计能力）和 几何图案 第四，使用数量性状基因座分析， 研究人员将测试240个匿名的，均匀分布的遗传基因的连锁。 左心室质量和几何模式的标记。 第五个目标是评估 基因与左心室肥大潜在危险因素之间的相互作用 （胰岛素、葡萄糖、血压对精神和身体压力的反应， 饮食和尿电解质、肥胖）和LV质量和几何形状。 建议的项目有以下优点：（i）纳入一个已 资助的研究，旨在检查。 高血压的遗传决定因素 (more超过500，000个个体基因型作为HyperGEN的一部分进行测量）; (ii)从正在进行的基于人群的研究中招募参与者， （三）与有经验的专家合作; 研究超声心动图的研究者，一位经验丰富的超声心动图 阅读中心（Richard Devereux博士指导下），统计学 关联和联系分析的专业知识（由D. C. Rao）， 和基因检测由国家的最先进的实验室（由博士指导， Lalouel）。 因此，这将是一个重要的和具有成本效益的 对LV遗传学知识和理解的贡献 肥厚