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Research core component: cardiovascular

$0P20FY2002MDNIH

North Carolina Central University, Durham NC

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Abstract

A multidisciplinary team has been assembled to identify gene polymorphisms and genomic loci that contribute to enhanced cardiovascular (CV) responses to stress in a college age African American population. This effort is based on the fact that for unknown reasons, African Americans suffer disproportionately from cardiovascular disease. The working hypothesis of the proposal is that there is a susceptible CV genotype in the African American population which displays enhanced CV reactivity to stress. This hypothesis will be tested by test pursuing the following specific aims. Specific aim 1 is to recruit a population of college age African American subjects and to perform phenotypic analysis of: (a) heart rate and blood pressure responses to acute mental stress; (a) heart rate and blood pressure responses to cold pressor stress; (c) the psychosocial characteristics of anxiety, hostility, depression, and stress; and (d) clinical characteristics that define individuals with metabolic syndrome. The data will be analyzed to define the distribution of each phenotype within the population and to calculate the correlation of occurrence of each trait relative to the others. These data will provide important new infbrmation about the occurrence of cardiovascular disease related phenotypes in this minority population. In addition, the study design will facilitate the sharing of data between this study and ongoing investigations being conducted by our collaborators using other African American populations. Specific aim 2 is to analyze DNA obtained from the population recruited in Specific Aim 1 to identify polymorphisms in candidate genes that associate with the defined phenotypes. This analysis will allow us to test the hypothesis that genetic variants are associated with increased cardiovascular reactivity to stress in this population and to define polymorphisms that also correlate with the psychosocial markers and metabolic phenotypes that have been linked with increased cardiovascular risk. Sets of candidate genes that will be studied include those which encode for gene products that are involved in sensory nerve transduction, sympathetic nerve transmission, the regulation of arterial contraction and relaxation, and CNS mediated responses to stress. It is anticipated that these studies will provide a critical test of the stated hypothesis; and the information that is generated may ultimately be used to allow identification of individuals with susceptible CV genotypes in other populations and direct the development of novel preventive strategies or medical interventions.

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