The overall goal of the research program is to characterize the interaction of psychosocial factors and susceptible genetic polymorphisms in contributing to the physiological blood pressure response to environmental stress and the subsequent development of hypertension in African Americans. This research problem is relevant to the clinical problem of disproportionately higher morbidity and mortality rates due to stroke, heart attacks, and end-stage renal disease seen in minority populations;diseases where hypertension is known to be a major risk factor. We propose that African Americans'physiological response to psychosocial stressors and ability to cope with these stressors contribute to elevated resting baseline blood pressures and that chronic exposure to the psychosocial stressors without appropriate coping skills play a significant part in the development of hypertension and cardiovascular disease. Therefore to determine if this is true, we propose the following Specific Aims: 1) to test the hypothesis that psychosocial factors significantly contribute to resting blood pressure in a cohort of 18-45 year-old African Americans, to test the hypothesis that the association of psychosocial factors and cardiovascular reactivity to psychological stress is dependent upon susceptible genetic polymorphisms in the (3-adrenergic pathway, and 3) to test the hypothesis that reactivity to psychological stressors is a better predictor of future elevation in resting blood pressure due to psychosocial factor modulation than reactivity to physiological stressors for African Americans. Four hundred African Americans will be recruited and blood pressure and heart rate response to acute psychological stress will be performed. Assessment of psychosocial factors (racism, hostility, John Henryism, anger, self-esteem, etc.) and DMA isolation for the determination of selected gene polymorphism using high through-put analysis will also be performed. The results from this study will provide what are, to our knowledge, the first characterizations of the selected candidate gene polymorphisms in an African American population and will thus provide important new information about susceptible gene polymorphisms. In addition, the results should provide important insight into the role of psychosocial factors in modulating behavior and known biological risk factors such as high cholesterol and insulin resistance. More importantly, the results will provide much needed information about how the stress of everyday living translates to increased risk of cardiovascular disease as a result of alterations in specific genes that regulate blood pressure response to stress.
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