Genetics of Cardiovascular Reactivity in Black Youth

黑人青年心血管反应性的遗传学

• 批准号: 7076131
• 负责人: BRUCE Stephen ALPERT
• 金额: $ 47.14万
• 依托单位: UNIVERSITY OF TENNESSEE HEALTH SCI CTR
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-07-05 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7076131
• 关键词: African American; adolescence (12-20); alpha adrenergic receptor; behavior test; behavioral /social science research tag; beta adrenergic receptor; blood pressure; cardiography; cardiovascular disorder risk; catecholamines; clinical research; disease /disorder onset; endocrine gland /system; essential hypertension; gene environment interaction; gene interaction; genetic polymorphism; genetic susceptibility; genotype; human subject; polymerase chain reaction; psychometrics; psychophysiology; racial /ethnic difference; renin angiotensin system; stress

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)：在美国黑人中，高血压(EH)的患病率和严重程度比美国其他种族更高。黑人因高血压(BP)而受到靶器官损害的风险增加，包括心脏病、中风和终末期肾功能衰竭。心血管对压力的反应性(CVR)存在显著的种族差异，这是导致血压升高的一个危险因素。我们和其他人已经证明，CVR对应激的影响随着时间的推移是稳定的，是可遗传的，并可以预测未来BP的升高和EH的发展。这些特性使CVR的测量成为高血压风险遗传学研究的有价值的中介。我们提出的假设是，黑人青年对急性应激的CVR个体差异与BP相关候选基因的明确多态有关，这些候选基因包括：1)α和β肾上腺素能受体基因；2)与儿茶酚胺代谢有关的基因；3)与内分泌功能有关的基因；4)与肾素血管紧张素系统有关的基因。通过关注血压正常的年轻人患高血压的风险，我们希望确定与高血压发病相关的基因，而不是高血压的后遗症。此外，由于急性应激的CVR被定义为由环境应激操作引起的心血管功能的变化，因此拟议的研究本质上是一项关于基因-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)，年龄在15-21岁之间。我们将收集口腔细胞样本，从所有受试者中提取DNA，进行遗传关联分析。我们将使用心阻抗图和血压监测来评估CVR在电子游戏、心算、冷加压和全身冷暴露任务中的应激成分，所有这些都是我们实验室已经利用或开发的。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额外基因-环境相互作用。我们计划将这个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人，从而促进EH的初级预防和/或早期治疗。