PSYCHOSOCIAL FACTORS AND SUSCEPTIBLE GENES INTERACTION IN CARDIOVASCULAR DISEASE

研究计划的总体目标是描述心理社会因素的相互作用， 易感基因多态性在促进生理血压反应， 非裔美国人的环境压力和随后的高血压发展。本研究 这一问题与发病率和死亡率不成比例地高的临床问题有关， 中风、心脏病发作和终末期肾病见于少数人群; 已知高血压是一个主要危险因素。我们认为非裔美国人的生理反应 心理社会压力源和科普这些压力源的能力有助于提高静息基线 血压和长期暴露于心理社会压力源而没有适当的应对技能， 在高血压和心血管疾病的发展中起重要作用。因此 为了确定这是否属实，我们提出以下具体目标：1）检验心理社会假设， 在一组18-45岁的非裔美国人中， 检验社会心理因素与心血管反应性之间的关系， 压力依赖于β-肾上腺素能途径中的易感基因多态性，以及3）测试 对心理应激的反应性是未来静息血液升高的更好预测因子的假设 压力，由于心理社会因素调制比反应性生理应激源，非洲 美国人将招募400名非裔美国人， 将进行急性心理应激试验。心理社会因素评估（种族主义、敌意、约翰 亨利主义、愤怒、自尊等）和DMA分离用于确定选定的基因多态性 还将进行使用高通量分析。这项研究的结果将提供什么是， 我们的知识，第一次表征选定的候选基因多态性在非洲 美国人群，从而提供了重要的新信息易感基因多态性。 此外，这些结果应该提供重要的洞察力的作用，心理社会因素在调节 行为和已知的生物风险因素，如高胆固醇和胰岛素抵抗。更重要的是， 研究结果将提供有关日常生活压力如何转化为 由于调节血液的特定基因的改变，导致心血管疾病的风险增加 压力对压力的反应。

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.