GENETICS, HOSTILITY & BIOLOGY OF STRESS IN DAILY LIFE

遗传学、敌意

• 批准号: 6831884
• 负责人: James D. Lane
• 金额: $ 15.38万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-12-01 至 2008-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6831884
• 关键词: African American; angers; behavioral /social science research tag; behavioral genetics; blood pressure; cardiovascular disorder risk; caucasian American; clinical research; gene environment interaction; gene expression; heart rate; human subject; lifestyle; stress

The goal of the Program Project is to identify genetic variations that interact with the environment to affect the expression and clustering of psychosocial and biobehavioral endophenotypes that increase cardiovascular disease (CVD). Exaggerated stress reactivity is likely to be an important CVD endophenotype. Evidence suggests that exaggerated reactivity is associated with increased CVD, and evidence suggests it has a genetic basis. Ambulatory measures of reactivity provide a crucial complement to laboratory studies because they demonstrate the ecological validity of the relationship of hostility and exaggerated reactivity in the environment where pathogenesis occurs. Project 3 will provide measurements of ambulatory stress reactivity for each of a sample of 400 probands (half African American and half Caucasian, half men and half women, and half scoring in the top and half in the bottom 20% on a valid, measure of hostility that predicts CVD and has heritability estimates of 40-55%) and at least one sibling for every proband, to make a total sample of 800-1200 subjects who will participate in the protocol of this project. These measurements will include blood pressure and heart rate variability, catecholamine and cortisol reactivity, and subjective stress and negative mood collected during a 24-hour period of normal daily activities in the natural environment. Both total variability and variability directly attributable to perceived stress and to negative mood will be available for cardiovascular measures, through the use of novel techniques of regression analysis. Neurohumoral activity will be determined by assay of urinary levels in daytime and overnight samples. Personal digital assistants (PDAs) will be used to collect subjective ratings during ambulatory monitoring. Our first goal will be to evaluate a minimum of 41 candidate genes/loci that act directly, in interaction with environmental factors, as a function of linkage disequilibrium with other sites, or membership in haplotypes, to influence hostility and ambulatory cardiovascular & neuroendocrine function. Collected ambulatory data will be combined with data from other Projects to determine genes/loci that affect the clustering of exaggerated ambulatory stress reactivity with hostility and other psychosocial and biobehavioral endophenotypes for CVD. In collaboration with the other Projects, Project 3 will advance our understanding of the genetic influences and gene/environment interactions that account for one of the most important CVD risk factors, hostility. The Projects will also explore how SES, sex and ethnicity may moderate the expression of involved genes. Program Project research activities will provide a comprehensive view of the clustering of CVD risk factors across multiple psychosocial and biobehavioral domains, which should lead to a clear understanding of the determinants of CVD and their genetic basis.

该计划项目的目的是确定与环境相互作用的遗传变异，以影响增加心血管疾病（CVD）的社会心理和生物行为内部型的表达和聚类。夸张的应激反应性可能是重要的CVD内表型。证据表明，夸张的反应性与CVD的增加有关，证据表明它具有遗传基础。反应性的卧床措施为实验室研究提供了至关重要的补充，因为它们证明了敌意与发病机理的环境中敌意与反应性夸大的关系的生态有效性。项目3将为400个样本（一半的非裔美国人和一半的高加索人，一半的男性和一半女性，一半在最底层和一半得分的有效的敌对措施，预测CVD，并且至少具有遗传性估计值40-55％），并在最低的20％中得分为20％，并在最低的20％中得分为40-55％），并在最低的20％中得分一半），为400个概率（一半的一半和一半的男性和一半）提供了卧床压力反应性的测量。 每一个证据，都是将参与该项目协议的800-1200名受试者的总样本。这些测量将包括血压和心率变异性，儿茶酚胺和皮质醇反应性，以及在自然环境中正常日常活动的24小时内收集的主观压力和负面情绪。通过使用新颖的回归分析技术，可用于心血管措施的总变异性和直接归因于感知应力和负面情绪的可变性。神经肿瘤活性将由白天和隔夜样品的尿液水平测定确定。个人数字助理（PDA）将用于在门诊监控期间收集主观评分。我们的第一个目标是评估至少41个候选基因/基因座，这些基因/基因座直接与环境因素相互作用，这是与其他站点不平衡的链接函数，或者是单倍型的成员资格，以影响敌意和卧床性心血管疾病。 神经内分泌功能。收集的卧床数据将与其他项目的数据相结合，以确定影响夸张的卧床压力反应性与敌对性以及其他心理社会和生物行为的内向型型CVD聚集的基因/基因座。与其他项目合作，项目3将促进我们对遗传影响和基因/环境相互作用的理解，这是最重要的 CVD风险因素，敌意。这些项目还将探讨SES，性别和种族如何减轻涉及基因的表达。计划项目研究活动将对多个社会心理和生物行为领域中CVD风险因素的聚类进行全面看法，这应该使人们对CVD的决定因素及其遗传基础有清晰的了解。