Genetics of Cardiovascular Reactivity in Black Youth

黑人青年心血管反应性的遗传学

• 批准号: 6771843
• 负责人: BRUCE Stephen ALPERT
• 金额: $ 46.71万
• 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/6771843
• 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）：黑人美国人中本质高血压（EH）的患病率和严重程度要比美国的其他种族较高，黑人对升高血压（BP）的靶心器官损害的风险增加，包括心脏病，中风和末期肾衰竭。压力的心血管反应性（CVR）存在很大的种族差异，这是BP升高的危险因素。我们和其他人表明，随着时间的流逝，CVR压力是稳定的，可遗传的，并且可以预测BP的未来升高和EH的发展。这些特性使CVR有价值的中间体用于高血压风险的遗传研究。我们建议检验以下假设：黑人青年中CVR与急性应激的个体差异与与BP相关的候选基因中定义明确的多态性有关，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）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。通过专注于有发育EH风险的正常青年，我们希望确定与高血压的发作而不是后遗症相关的基因。此外，鉴于CVR到急性应力的定义是通过对压力的环境操纵引起的心血管功能的变化，因此拟议的研究本质上是对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（男性和女性的数量相等），15-21岁。我们将收集从所有受试者中提取DNA的颊细胞样品进行遗传关联分析。我们将使用阻抗心脏摄影和BP监测来评估CVR的组成部分，以在视频游戏，心理算术，冷压力和全身冷曝光任务期间进行压力，所有这些任务均已在我们的实验室中使用或开发。我们将使用各种方法将与CVR的遗传关联评估为急性应激，包括对单核苷酸多态性和单倍型的分析。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压力的其他基因 - 环境相互作用。我们计划将来自该项目的数据与来自西班牙裔和非西班牙裔白人的未来研究的数据进行比较。这项研究的结果可能有助于早期鉴定出高血压风险增加的个体，从而促进原发性预防和/或EH的早期治疗。