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Genetics of Cardiovascular Reactivity in Black Youth

黑人青年心血管反应性的遗传学

基本信息

批准号：
7254040
负责人：
BRUCE Stephen ALPERT
金额：
$ 42.57万
依托单位：
UNIVERSITY OF TENNESSEE HEALTH SCI CTR
依托单位国家：
美国
项目类别：
财政年份：
2003
资助国家：
美国
起止时间：
2003-07-05 至 2009-06-29
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7254040
关键词：
ADRB2 gene Acute Adolescence Adolescent Adrenergic Agents Adrenergic Receptor Adult African American Age Age-Years Blood Pressure Blood Pressure Monitors Body mass index Candidate Disease Gene Cardiac Cardiovascular Physiology Cardiovascular system Catecholamines Cells Cerebrovascular Disorders Child Childhood Chronic Coronary heart disease DNA Data Development Diastolic blood pressure Disease Disease model Disease susceptibility Early identification Early treatment Elevation End stage renal failure Endocrine Essential Hypertension Ethnic group Female Fostering Future Genes Genetic Genetic Polymorphism Genetic Research Genetic Variation Haplotypes Heart Diseases Hispanics Hypertension Impedance Cardiography Incidence Individual Individual Differences Institutes Investigation Laboratories Measures Metabolism Methods Not Hispanic or Latino Numbers Onset of illness Organ Peripheral Resistance Phenotype Physiological Prevalence Prevention intervention Primary Prevention Property Psyche structure Race Renin-Angiotensin System Research Rest Risk Risk Factors Rural Population Sampling Severities Single Nucleotide Polymorphism Socioeconomic Status Stress Stroke System Testing Time United States Video Games Youth acute stress adrenergic blood pressure regulation cardiovascular risk factor ethnic difference gene environment interaction gene interaction genetic association male normotensive racial difference response reuptake sex stressor young adult

项目摘要

DESCRIPTION (provided by applicant): The prevalence and severity of essential hypertension (EH) are greater among Black Americans than other ethnic groups in the U.S. Blacks are at increased risk for target organ damage from elevated blood pressure (BP), including heart disease, stroke, and end-stage renal failure. There are significant ethnic differences in cardiovascular reactivity (CVR) to stress, which is a risk factor for elevated BP. We and others have shown that CVR to stress is stable over time, heritable, and predictive of future elevations in BP and the development of EH. These properties make measures of CVR valuable intermediate for genetic studies of hypertensive risk. We propose to test the hypothesis that individual differences in CVR to acute stress in Black youth are associated with well-defined polymorphisms in candidate genes related to BP including: 1) alpha- and beta-adrenergic receptor genes; 2) genes involved in catecholamine metabolism; 3) genes involved in endocrine function; 4) genes involved in the renin angiotensin system. By focusing on normotensive youth at risk for developing EH, we hope to identify genes associated with the onset, rather than the sequelae, of hypertension. Moreover, given that CVR to acute stress is defined as a change in cardiovascular function evoked by an environmental manipulation of stress, the proposed research is inherently a study of gene-environment interactions. We will study 500 unrelated Black adolescents and young adults (equal numbers of males and females), 15-21 years of age. We will collect buccal cell samples for DNA extraction from all subjects for genetic association analyses. We will use impedance cardiography and BP monitoring to assess components of CVR to stress during video game, mental arithmetic, cold pressor, and whole body cold exposure tasks, all of which have been utilized or developed in our laboratory. We will use various methods to evaluate genetic associations with CVR to acute stress, including analyses of single nucleotide polymorphisms and haplotypes. Supplementary analyses will evaluate potential gene-gene interactions and additional gene-environment interactions involving chronic environmental stress. We plan to compare data from this project to data from future studies of Hispanic and non-Hispanic Whites. The results of this study may aid in the early identification of individuals at increased risk for hypertension, thus fostering primary prevention and/or early treatment of EH.

描述（由申请人提供）：美国黑人原发性高血压（EH）的患病率和严重程度高于美国其他种族。黑人血压升高（BP）导致靶器官损伤的风险增加，包括心脏病、中风和终末期肾衰竭。心血管反应性（CVR）对压力的反应存在显著的种族差异，这是血压升高的风险因素。我们和其他人已经表明，CVR压力是稳定的，随着时间的推移，可遗传，并预测未来的血压升高和高血压的发展。这些特性使得CVR的测量对于高血压风险的遗传研究是有价值的中间体。我们建议检验这一假设，即黑人青年急性应激CVR的个体差异与BP相关候选基因的明确多态性相关，包括：1）α和β肾上腺素能受体基因; 2）参与儿茶酚胺代谢的基因; 3）参与内分泌功能的基因; 4）参与肾素血管紧张素系统的基因。通过关注血压正常的年轻人，我们希望能够确定与高血压发病相关的基因，而不是高血压后遗症。此外，鉴于急性应激的CVR被定义为由应激的环境操纵引起的心血管功能的变化，因此所提出的研究本质上是基因-环境相互作用的研究。我们将研究500名无关的黑人青少年和年轻人（男女人数相等），15-21岁。我们将从所有受试者中收集颊细胞样本用于DNA提取，以进行遗传关联分析。我们将使用阻抗心动图和BP监测来评估CVR的组成部分，以在视频游戏，心算，冷加压和全身冷暴露任务中施加压力，所有这些都已在我们的实验室中使用或开发。我们将使用各种方法来评估CVR与急性应激的遗传关联，包括单核苷酸多态性和单倍型分析。补充分析将评估潜在的基因-基因相互作用和涉及慢性环境应激的其他基因-环境相互作用。我们计划将该项目的数据与未来对西班牙裔和非西班牙裔白人的研究数据进行比较。这项研究的结果可能有助于早期识别高血压风险增加的个体，从而促进高血压的一级预防和/或早期治疗。