FAMILIAL DILATED CARDIOMYOPATHY--DETECTION/GENE MAPPING

家族性扩张型心肌病——检测/基因图谱

• 批准号: 6184193
• 负责人: RAY E. HERSHBERGER
• 金额: $ 49.36万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-05-01 至 2002-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6184193
• 关键词: African American; clinical research; disease /disorder etiology; echocardiography; family genetics; gene expression; genetic mapping; heart ventricle; human subject; idiopathic dilated cardiomyopathy; linkage mapping

DESCRIPTION: (Adapted from Investigator's Abstract) Heart failure is the only major cardiovascular diagnosis increasing in incidence and prevalence in the U.S., and it affects more than two million citizens. Heart failure causes a great deal of morbidity, carries a high mortality rate and consumes considerable health care resources. Heart failure is the single most expensive diagnosis related group (DRG 127) in the Health Care Financing Administration (HCFA) Medicare budget (1992 data), due in substantial part to the high incidence and prevalence of heart failure in aging Americans. Despite this accelerating and costly public health problem, two decades of intensive basic and clinical investigations have not yielded a unifying pathophysiological concept, and the underlying molecular mechanisms of heart failure are still unknown. The most common type of heart failure is dilated cardiomyopathy, and one common form is idiopathic dilated cardiomyopathy (IDC). It has recently been shown that 20-30% of patients with IDC have family members similarly affected. This condition, termed familial dilated cardiomyopathy (FDC), suggests that an underlying molecular mechanism may be involved. Indeed, four groups have recently reported linkage in large families with FDC, suggesting that FDC is likely a genetic disease. The application suggests that identification of a disease-associated gene could provide a significant improvement of understanding the mechanisms of heart failure. Since 1993, the Oregon Health Sciences University (OHSU) has prospectively identified numerous families with FDC. The application suggests that the selection of three large pedigrees would be useful for clinical and gene mapping studies. The Specific Aims of this project are to: 1) perform extensive clinical screening and characterization of OHSU FDC-3, a very large African-American family with dilated cardiomyopathy, using echocardiographically-derived left ventricular dimensions to classify members as affected or non-affected. To date, no other African-American family has been characterized with FDC. Black Americans demonstrate considerable excess cardiovascular mortality and have traditionally been underrepresented in clinical research; and 2) map the gene or genes responsible for FDC in OHSU families FDC-1, FDC-2 and FDC-3. Preliminary data suggest that OHSU FDC-1 links to neither of the recently reported cardiomyopathy chromosomal locations, suggesting that an additional locus for FDC is present.

描述：（根据调查员的摘要改编）心力衰竭是 只有主要心血管诊断的发病率和患病率增加 在美国，它影响了超过200万公民。 心脏衰竭 引起大量发病率，具有高死亡率，并消耗 大量的医疗保健资源。 心力衰竭是最单身的 昂贵的诊断相关组（DRG 127） 管理（HCFA）Medicare预算（1992年数据），在很大程度上应有 衰老的美国人心力衰竭的发病率和患病率很高。 尽管加速且昂贵的公共卫生问题，但二十年 密集的基本和临床研究尚未产生统一 病理生理概念以及心脏的基本分子机制 失败仍然未知。 最常见的心力衰竭类型是扩张的 心肌病，一种常见的形式是特发性扩张的心肌病 （IDC）。 最近已显示20-30％的IDC患者患有 家庭成员类似地影响。 这种情况称为家族性扩张 心肌病（FDC）表明，潜在的分子机制可能是 涉及。 确实，四个小组最近报告了大型联系 FDC的家庭表明FDC可能是一种遗传疾病。 这 应用表明，鉴定与疾病相关的基因可以 提供理解心脏机制的重大改进 失败。 自1993年以来，俄勒冈健康科学大学（OHSU）拥有 前瞻性地确定了许多FDC的家庭。 应用程序 建议选择三种大型血统对 临床和基因映射研究。 该项目的具体目的是 至：1）进行OHSU的广泛临床筛查和表征 FDC-3，一个非常大的非裔美国人家庭，患有扩张的心肌病， 使用超声心动图衍生的左心室尺寸进行分类 成员受到影响或不受影响的成员。 迄今为止，没有其他非裔美国人 家庭的特征是FDC。 黑人美国人证明 大量过量的心血管死亡率，传统上是 临床研究的代表性不足； 2）映射基因或基因 负责OHSU家族FDC-1，FDC-2和FDC-3的FDC。 初步的 数据表明OHSU FDC-1链接到最近报道的 心肌病染色体位置，表明一个额外的基因座 对于FDC存在。