Genes of Oxidative Stress and Atherosclerotic Complications of Hypertension

描述(申请人提供)：动脉粥样硬化是冠状动脉疾病(CAD)的主要原因，冠心病是美国男性和女性的最大杀手。氧化应激导致内皮功能障碍是高血压导致动脉粥样硬化过程的一个潜在因素。这项名为“高血压的氧化应激和动脉粥样硬化并发症的基因”的项目旨在研究氧化应激途径基因变异在冠状动脉钙化(CAC)遗传结构中的作用。CAC是一种衡量亚临床冠状动脉粥样硬化的指标。这项研究项目将使用基因网络方法来识别影响冠状动脉抵抗高血压损伤能力的基因。所有DNA资源、CAD风险因素、体检数据和CAC措施已经从三个队列中提供给这个项目。基因多态、协变量、高血压和亚临床冠状动脉粥样硬化之间的假设关系的模型将使用CAC进行评估，CAC已经在有个人或家族高血压病史的个人身上进行了测量，这些个人或家族来自明尼苏达州罗切斯特的动脉病遗传流行病学网络中心，以及来自同样来自明尼苏达州罗切斯特的冠状动脉钙化流行病学(ECAC)研究的有高血压个人或家族史的个人。将在动脉粥样硬化多种族研究(MESA)的个体中寻求重复的研究结果的概括性。我们将使用这种基于氧化应激基因网络的方法来超越单一的多态效应，并研究单基因、基因间的相互作用和基因间的环境相互作用如何结合起来影响高血压患者或高血压风险增加的个体的CAC数量。 公共卫生相关性 动脉粥样硬化是冠状动脉疾病(CAD)的主要原因，冠心病是美国男性和女性的最大杀手。加深我们对基因变异在不同人群亚临床冠状动脉粥样硬化中的作用的了解，有助于及早识别临床疾病易感性增加的个体，开发新的、更有效的治疗方法，并为最有可能反应的人量身定做治疗方法。

DESCRIPTION (provided by applicant): Atherosclerosis is the major cause of coronary artery disease (CAD), the single largest killer of American men and women. Oxidative stress leading to endothelial dysfunction is an underlying factor whereby hypertension contributes to the atherosclerotic process. This project entitled "Genes of Oxidative Stress and Atherosclerotic Complications of Hypertension" proposes to characterize the role of oxidative stress pathway gene variation in the genetic architecture of coronary artery calcification (CAC), a measure of subclinical coronary atherosclerosis. This research project will use a gene network approach to identify genes that influence the ability of the coronary artery to resist injury due to hypertension. All DNA resources, CAD risk factors, physical examination data and CAC measures are already available to this project from three cohorts. Models of the hypothesized relationships between genetic polymorphisms, covariates, hypertension and subclinical coronary atherosclerosis will be evaluated using CAC, already measured on individuals with a personal or family history of essential hypertension from the Genetic Epidemiology Network of Arteriopathy (GENOA), Rochester, MN fieldcenter and on individuals with a personal or family history of hypertension from the Epidemiology of Coronary Artery Calcification (ECAC) study, also from Rochester, MN. The generalizability of findings which replicate will be sought in the individuals of the Multi-Ethnic Study of Atherosclerosis (MESA). We will use this oxidative stress gene network-based approach to move beyond single polymorphism effects and investigate how single-genes, gene-by-gene interactions and gene-by-environment interactions combine to influence CAC quantity in individuals with hypertension or at increased risk of hypertension. PUBLIC HEALTH RELEVANCE Atherosclerosis is the major cause of coronary artery disease (CAD), the single largest killer of American men and women. Increasing our understanding of the role of genetic variation in sub-clinical coronary atherosclerosis in diverse populations can contribute to the earlier identification of individuals with increased susceptibility to clinical disease, the development of new, more efficacious treatments, and tailoring of treatments to those most likely to respond.