Social, Genetic Determinants of Blood Pressure in Underserved African Americans

描述（由申请人提供）：高血压（BP）在美国高达78%的老年人中存在，在非裔美国人中比其他种族群体更普遍，并且是心血管疾病死亡的主要原因。社会-环境压力和社会支持因素，如个人社会经济地位（SES），与高血压有关，还有相关的生理机制，如下丘脑-垂体-肾上腺（HPA）分泌的糖皮质激素应激激素（如皮质醇），以及遗传因素，如糖皮质激素受体（GR）基因多态性。然而，很少有研究将这些因素整合到非裔美国人身上，而且社会环境因素通常是在个人层面上测量的，而不是在社区层面上测量的，这使得人们对社区因素（如社区SES）在人群层面上理解BP调节机制和健康差异的相关努力的了解很少。研究这些因素如何相互作用影响BP的结果，可以更好地了解BP的病因，并有助于成功预防。此外，生态学、社会心理和生物学的健康理论可以指导这种综合调查。因此，本研究的目的是研究社区水平的社会环境因素如何与GR多态性相互作用，以预测皮质醇和高血压，以及皮质醇是否介导了社会环境因素与血压的关联，作为一种潜在的生理机制，这已经在临床和实验模型中得到了很好的证实。每个变量的数据将在现有的非洲裔美国老年人样本（N=434；年龄=51.2岁）中收集，这些样本嵌套在三个社区中，作为正在进行的美国国立卫生研究院资助的PATH试验的一部分。试验的PI，道恩·威尔逊博士，是这项申请的主要发起人。参与者将参加健康检查，在此期间将收集目标变量的数据。社会环境变量将包括通过调查问卷测量的人口普查得出的社区水平SES、社区犯罪率和社区连通性。唾液样本将允许测量上午和下午的皮质醇作为基础下丘脑功能和压力的标志。将从口腔拭子样本中提取先前与高血压的社会环境和生理机制相关的三个单核苷酸多态性（Bcl1, rs 41423247; FKBP5, rs1360780; 92, rs6198）的基因组DNA，并在本申请的共同申办者Matthew Kostek博士的指导下，通过聚合酶链反应进行检测。结构方程建模和回归将用于检验既定的研究目标和假设，统计模型中包括相关协变量，如血压用药状况、年龄和性别。通过检测类内相关系数来控制潜在的群体聚类。因此，通过对社会环境、生理和遗传因素的综合研究，本研究将有助于对服务不足的非裔美国人群的高血压和差异有一个全面的概念，并有可能为创新的预防方法和公共政策提供信息。

DESCRIPTION (provided by applicant): High blood pressure (BP) is present in up to 78% of older adults in the United States, is more prevalent in African Americans than other ethnic groups, and is a leading cause of cardiovascular disease mortality. Social- environmental stress and social support factors, such as individual socioeconomic status (SES), have been linked to high BP, as have related physiological mechanisms such as hypothalamic-pituitary-adrenal (HPA) secretion of glucocorticoid stress hormones (e.g. cortisol), and genetic factors such as polymorphisms in glucocorticoid receptor (GR) genes. However, few studies have integrated these factors in African Americans, and social-environmental factors have often been measured at the individual- but not at the community-level, giving little insight into community factors (e.g. community SES) relevant to population-level efforts to understand BP regulatory mechanisms and health disparities. Investigating how these factors interact to influence BP outcomes may afford a better understanding of BP etiology and contribute to successful prevention efforts. Additionally, ecological, psychosocial, and biological theories of health may guide such an integrated investigation. Thus, the aim of the proposed study is to examine how community-level social- environmental factors interact with GR polymorphisms to predict cortisol and high BP, and whether cortisol mediates the association of social-environmental factors with BP as an underlying physiologic mechanism, as has been well established in clinical and experimental models. Data for each variable will be collected within an existing sample of older adult African Americans (N=434; Mage=51.2 years) nested within three communities as part of the on-going NIH-funded PATH trial. The PI of the trial, Dr. Dawn Wilson, is the primary sponsor of this application. Participants will attend health screenings during which data for target variables will be collected. Social-environmental variables will include census-derived community-level SES, community crime rates, and community connectedness measured via questionnaire. Saliva samples will allow measurement of morning and afternoon cortisol as a marker of basal HPA functioning and stress. Genomic DNA for three single nucleotide polymorphisms (SNPs) previously linked to social-environmental and physiologic mechanisms of high BP (Bcl1, rs 41423247; FKBP5, rs1360780; 92, rs6198) will be extracted from buccal swab samples and assayed via polymerase chain reaction, under the guidance of Dr. Matthew Kostek, a co-sponsor of this application. Structural equation modeling and regression will be applied to test stated study aims and hypotheses, with relevant covariates such as BP medication status, age, and sex included in statistical models. Potential clustering by community will be controlled by examining intra-class correlation coefficients. Thus, through the integrated study of social-environmental, physiologic, and genetic factors, this investigation will contribute to a comprehensive conceptualization of high BP and disparity in underserved African American populations, and has the potential to inform innovative prevention approaches and public policy.