Genetics of Cardiovascular Reactivity in Black Youth

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种族。黑人因血压升高（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。心血管对压力的反应性（CVR）是血压升高的危险因素，种族间存在显著差异。我们和其他研究人员已经表明，CVR对压力随时间的推移是稳定的、可遗传的，并且可以预测未来BP升高和EH的发展。这些特性使得测量CVR对高血压风险的遗传研究有价值。我们建议检验黑人青年急性应激CVR的个体差异与BP相关候选基因的明确多态性相关的假设，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。通过关注血压正常且有发生EH风险的青少年，我们希望确定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，考虑到急性应激的CVR被定义为由环境操纵压力引起的心血管功能变化，本研究本质上是对基因-环境相互作用的研究。我们将研究500名无血缘关系的15-21岁黑人青少年和年轻人（男女人数相等）。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CVR组件在视频游戏、心算、冷压和全身冷暴露任务中的压力，所有这些都是我们实验室已经使用或开发的。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-基因相互作用和其他涉及慢性环境应激的基因-环境相互作用。我们计划将这个项目的数据与未来西班牙裔和非西班牙裔白人研究的数据进行比较。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，从而促进初级预防和/或早期治疗EH。

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.