Genes of Oxidative Stress and Atherosclerotic Complications of Hypertension

氧化应激基因和高血压动脉粥样硬化并发症

基本信息

批准号：
8269611
负责人：
JAMES E. HIXSON
金额：
$ 37.8万
依托单位：
UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-07-01 至 2014-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8269611
关键词：
African American Age Alcohol consumption American Architecture Arterial Disorder Atherosclerosis Body Size Chinese People Clinical Coronary Arteriosclerosis Coronary artery DNA Data Development Disease Early identification Epidemiology Essential Hypertension Family history of Functional disorder Gender Genes Genetic Genetic Polymorphism Genetic Risk Genetic Variation Hispanics Hypertension Individual Inflammation Injury Measures Modeling Network-based Not Hispanic or Latino Oxidative Stress Oxidative Stress Pathway Participant Pathway interactions Pharmaceutical Preparations Physical Examination Play Population Heterogeneity Predisposition Process Race Research Research Project Grants Resources Risk Risk Factors Role Sampling Single Nucleotide Polymorphism Smoking Testing Variant Woman cohort coronary artery calcification disorder risk gene environment interaction gene interaction genetic epidemiology men public health relevance

项目摘要

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.

描述（由申请人提供）：动脉粥样硬化是冠状动脉疾病（CAD）的主要原因，冠状动脉疾病是美国男性和女性最大的杀手。导致内皮功能障碍的氧化应激是高血压有助于动脉粥样硬化过程的潜在因素。该项目标题为“高血压的氧化应激基因和动脉粥样硬化并发症”提出了表征氧化应激途径基因变异在冠状动脉钙化遗传结构（CAC）中的作用，这是次级冠状动脉粥样硬化的量度。该研究项目将使用一种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。该项目的所有DNA资源，CAD风险因素，体格检查数据和CAC度量已经从三个同类中获得。 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冠状动脉钙化（ECAC）研究，也来自明尼苏达州罗切斯特。在动脉粥样硬化（MESA）的多种族研究的个体中，将寻求复制的发现的普遍性。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多态性效应，并研究单生，基因相互作用和逐个环境相互作用如何影响高血压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，冠状动脉疾病是美国男性和女性的最大杀手。我们对遗传变异在不同种群中遗传变异的作用的理解可以促进对临床疾病易感性增加的个体的早期鉴定，新的，更有效的治疗方法的发展以及对最有可能反应者的治疗量身定制的治疗方法。