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）：美国黑人中原发性高血压 (EH) 的患病率和严重程度高于美国其他族裔群体。黑人因血压 (BP) 升高而遭受靶器官损害的风险更高，包括心脏病、中风和终末期肾衰竭。心血管对压力的反应性（CVR）存在显着的种族差异，这是血压升高的危险因素。我们和其他人已经证明，随着时间的推移，压力的 CVR 是稳定的、可遗传的，并且可以预测未来血压升高和 EH 的发展。这些特性使得 CVR 测量成为高血压风险遗传研究的宝贵中间体。我们建议检验以下假设：黑人青少年急性应激 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）涉及内分泌功能的基因； 4) 参与肾素血管紧张素系统的基因。通过关注有患 EH 风险的血压正常青少年，我们希望找出与高血压发病相关的基因，而不是与高血压后遗症相关的基因。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，因此拟议的研究本质上是基因与环境相互作用的研究。我们将研究 500 名无亲属关系的 15-21 岁黑人青少年和年轻人（男性和女性人数相等）。我们将收集所有受试者的口腔细胞样本，提取 DNA，进行遗传关联分析。我们将使用阻抗心动图和血压监测来评估视频游戏、心算、冷加压和全身冷暴露任务期间 CVR 的压力组成部分，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 EH 的一级预防和/或早期治疗。