Genomics of Peripheral Arterial Disease

外周动脉疾病的基因组学

• 批准号: 6908725
• 负责人: Jeffrey H. Lawson
• 金额: $ 15.4万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-04-06 至 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6908725
• 关键词: amputation; aorta disorder; artery occlusion; atherosclerosis; biotechnology; clinical research; comparative genomic hybridization; data collection; gene expression profiling; genetic registry /resource /referral center; genome; human subject; human tissue; information retrieval; microarray technology; molecular biology information system; pathologic process; peripheral blood vessel disorder; phenotype; statistics /biometry

DESCRIPTION (provided by applicant): Peripheral arterial disease (PAD) is a complex illness causing a significant amount of pain and suffering, with an estimated 8-12 million cases in the United States. The elderly are particularly at risk, with a prevalence of approximately 20% in people greater than 75 years of age. Further, the number of cases is expected to increase as the population ages. PAD exerts significant effects on functional capacity, quality of life, productivity, and health care costs. This R21 Grant application was developed to address the genetic basis of PAD using existing and novel data sets and tissue samples. Recent sequencing of the human genome has opened up fertile areas of investigation for many human diseases. To date, there have been a limited number of studies that have investigated the genetic underpinnings of PAD. Fundamental advancements in our knowledge of the molecular pathophysiology of PAD utilizing genome technologies represents an unprecedented opportunity to develop new diagnostic, prognostic and therapeutic interventions for this disease. To address this problem, we have developed a unique research group that combines the collaborative expertise of vascular surgery, molecular cardiology, biostatistics, and human genetics. In this application we propose to investigate PAD using genomic methodology. We have assembled all of the necessary components with direct access to human peripheral arteries, a large clinical population with PAD, experience with gene expression profiling, and the advanced statistical analysis required to study this complex disease. Using this methodology, we propose to use expression genomic s on peripheral arterial tissue collected from limb amputations in patients with severe PAD. Using data derived from these arterial samples we will test the following hypotheses: 1. Gene expression profiles of peripheral arterial tissues can be used to identify molecular phenotypes of diseased arteries. 2. Various phenotypes of patients with PAD will have different patterns of gene expression. 3 Genes isolated from diseased peripheral arteries will differ from key genes that have been identified from existing data sets for central (aortic) atherosclerosis. To achieve these goals, the following specific aims will be pursued: 1. To isolate arterial tissue from amputated limbs and collect clinical data from these patients with severe PAD. 2. To perform gene expression analysis using microarrays on RNA extracted from harvested peripheral arterial tissues. 3. To apply statistical methods to identify gene expression patterns that correlate with the clinical phenotypes of patients with PAD and compare these expression patterns to existing identified genes of aortic atherosclerosis.

描述（由申请人提供）：周围动脉疾病（PAD）是一种复杂的疾病，导致了大量的疼痛和痛苦，估计在美国估计有8-12万例。老年人特别有风险，大于75岁的人的患病率约为20％。此外，随着人口年龄的增长，预计病例的数量将增加。 PAD对功能能力，生活质量，生产力和医疗保健成本产生重大影响。该R21赠款的应用是为了使用现有和新颖的数据集和组织样本来解决PAD的遗传基础。最近对人类基因组的测序为许多人类疾病打开了肥沃的研究领域。迄今为止，已经进行了有限的研究研究了PAD的遗传基础。我们对使用基因组技术的PAD分子病理生理学了解的基本进步是为这种疾病开发新的诊断，预后和治疗性干预措施的前所未有的机会。为了解决这个问题，我们开发了一个独特的研究小组，该小组结合了血管外科，分子心脏病学，生物统计学和人类遗传学的协作专业知识。在此应用中，我们建议使用基因组方法研究PAD。我们已经组装了所有必要的组成部分，直接进入人类外围动脉，具有PAD的大量临床人群，具有基因表达分析的经验以及研究这种复杂疾病所需的先进统计分析。使用这种方法，我们建议在严重PAD患者的肢体截肢中收集的外周动脉组织上使用表达基因组S。使用从这些动脉样本得出的数据，我们将测试以下假设：1。外周动脉组织的基因表达谱可用于鉴定疾病动脉的分子表型。 2。患有PAD患者的各种表型将具有不同的基因表达模式。从患病的周围动脉分离的3个基因将与已从中心（主动脉）动脉粥样硬化的现有数据集中鉴定出的关键基因不同。为了实现这些目标，将追求以下特定目标：1。将动脉组织从截肢的肢体中分离出来，并从这些严重PAD患者那里收集临床数据。 2。使用微阵列对从收获的周围动脉组织提取的RNA上进行基因表达分析。 3。应用统计方法来识别与PAD患者的临床表型相关的基因表达模式，并将这些表达模式与主动脉粥样硬化的现有鉴定基因进行比较。