Race, HTN, and Vascular Adrenoceptor Gene Expression

描述（由申请人提供）：高血压（HTN）具有复杂的表型，具有许多临床变异，使疾病管理复杂化。与其他种族相比，非裔美国人（AA）表现出最高的HTN率和最差的健康结果。可能导致种族特异性健康和疾病结局差异的可能因素集中在社会经济因素以及病理生理机制、药理学反应和最近的遗传变异性差异上。动物模型基因表达研究的新发现使一些人怀疑基因表达（mRNA量的测量）在HTN中的作用的可能性很大。申请方提议检查人种和α-1A-和β-2-肾上腺素能受体（ADR）的基因表达在人HTN中的作用。申请人还将检查α-1A-和β-2-ADR基因表达水平与血管张力之间的关系。这将是一项四臂基因表达研究，主要比较来自两个种族类别-非洲裔美国人和高加索人的HTN患者和非HTN患者。预计共28例受试者，每组7例受试者，具体研究目的如下：1）收集冠状动脉旁路移植术（CABG）患者丢弃的左乳内动脉（LIMA）组织残留物，分析不同种族和诊断的组织中α-1A-和β-2-ADR基因表达的差异;和2）比较来自给药前和给药后的手术后总外周阻力（TPR）平均值。

DESCRIPTION (provided by applicant): Hypertension (HTN) has a complex phenotype with many clinical variations that complicate disease management. African Americans (AA) exhibit the highest rate of HTN and the worst health outcomes, compared to other races. The possible factors that may contribute to race-specific differences in health and disease outcomes have centered around socioeconomic factors as well as differences in pathophysiologic mechanisms, pharmacologic responses, and recently, genetic variability. New findings in gene expression research with animal models have led some to suspect a great possibility for gene expression (measure of mRNA quantity) in the role of HTN. The applicant proposes to examine the roles that race and gene expression of the alpha-1A- and beta-2-adrenergic receptors (ADRs) play in human HTN. The applicant will also examine the relationship between level of alpha-1A- and beta-2-ADR gene expression and vascular tone. This will be a four-arm gene expression study that will primarily compare persons with and without HTN from two race categories -- African Americans and Caucasians. A total of 28 subjects are anticipated with 7 subjects in each arm. The specific aims of the study will be accomplished by: 1) Collecting left internal mammary artery (LIMA) tissue remnants discarded from coronary artery bypass graft (CABG) patients, and analyzing the tissue for differences in gene expression of the alpha-1A- and beta-2-ADR genes by race and diagnosis; and 2) Comparing post-operative total peripheral resistance (TPR) averages from pre- and post-inotrope administration.