Genetics of Cardiovascular Reactivity in Black Youth

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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.