PSYCHOSOCIAL FACTORS AND SUSCEPTIBLE GENES INTERACTION IN CARDIOVASCULAR DISEASE

该研究计划的总体目标是描述心理社会因素和 易感基因多态对生理性血压反应的影响 环境压力与非裔美国人高血压的后续发展。这项研究 这一问题与临床问题有关，即由于以下原因导致的发病率和死亡率高得不成比例 在少数民族人群中可见的中风、心脏病发作和终末期肾病； 众所周知，高血压是一个主要的危险因素。我们认为非裔美国人的生理反应 心理社会压力源和应对这些压力源的能力有助于提高静息基线 血压和长期暴露在没有适当应对技能的心理社会应激源中 在高血压和心血管疾病的发展中起着重要作用。因此，要 确定这是否属实，我们提出了以下具体目标：1)检验心理社会假说 在18-45岁的非裔美国人队列中，因素对静息血压有显著影响 检验心理社会因素和心血管反应性与心理健康的关系 应激依赖于(3-肾上腺素能途径)中的易感遗传多态，以及3)测试 假设对心理应激源的反应性是未来静息血液中升高的更好的预测因子 非洲人由于心理社会因素调节而不是对生理应激源的反应而产生的压力 美国人。400名非洲裔美国人将被招募，血压和心率对 将进行急性心理应激。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分离用于确定所选基因的多态性 还将执行使用高吞吐量分析。这项研究的结果将提供以下内容： 我们的知识，首次描述了非洲人所选择的候选基因的多态性 因此，将提供有关易感基因多态的重要新信息。 此外，研究结果应该为心理社会因素在调节中的作用提供重要的见解。 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， 研究结果将提供关于日常生活压力如何转化为 因调节血液的特定基因改变而增加心血管疾病的风险 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.