CLINICAL TRIAL: PHARMACOGENOMIC EVALUATION OF ANTIHYPERTENSIVE RESPONSES (PEAR)

临床试验：抗高血压反应的药物基因组学评估（梨）

• 批准号: 7717108
• 负责人: Julie E. Johnson
• 金额: $ 16.37万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-12-01 至 2008-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7717108
• 关键词: Adrenergic beta-Antagonists; Antihypertensive Agents; Atenolol; Candidate Disease Gene; Chronic Disease; Clinical Trials; Combined Modality Therapy; Computer Retrieval of Information on Scientific Projects Database; Contrast Media; Data; Diuretics; Drug Prescriptions; Evaluation; Exhibits; Funding; Genes; Genetic; Genetic Variation; Grant; Health Care Costs; Heart failure; Human Genome; Hydrochlorothiazide; Hypertension; Individual; Institution; Kidney Failure; Lead; Lipids; Measures; Metabolic; Mono-S; Myocardial Infarction; Outcome; Pharmaceutical Preparations; Pharmacogenetics; Pharmacogenomics; Pharmacotherapy; Phenotype; Polypharmacy; Rate; Research; Research Personnel; Resources; Risk Factors; Source; Stroke; Testing; Thiazide Diuretics; Uncomplicated Hypertension; United States National Institutes of Health; Variant; genetic association; improved; insulin sensitivity; novel; response

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Hypertension (HTN) is the most common chronic disease for which drugs are prescribed, and the most prevalent risk factor for heart attack, stroke, renal failure and heart failure. Responses to antihypertensive drug therapy exhibit considerable interpatient variability, contributing to poor rates of HTN control. We propose to identify genetic predictors of the antihypertensive and adverse metabolic responses to two preferred and pharmacodynamically contrasting drugs, a beta-blocker (atenolol) and a thiazide diuretic (HCTZ) given initially as monotherapy, and subsequently in combination, to 800 individuals with uncomplicated hypertension. High quality phenotype data response, lipid and insulin sensitivity measures of adverse metabolic responses will be related to genetic variation through two approaches. First, testing 7 SNPs in each of 70 candidate genes, we will examine the influence of these genes-variation on responses to beta-blockers and diuretics. This will include assessment of genetic associations with: antihypertensive responses to monotherapy, addition of a second drug to monotherapy, and combination therapy and adverse metabolic responses to mono and combination therapy. This candidate gene approach will be supplemented by discovery of novel genes involved in variable BP and metabolic responses to beta-blockers and diuretics through testing of 20,000 pututative functional SNPs that span the human genome. The proposed research will substantially increase our understanding of the pharmacogenetics of mono- and combination antihypertensive drug therapy. This would likely lead to higher rates of HTN control, less need for polypharmacy, reduced health care costs, and improved outcomes.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 高血压（HTN）是最常见的慢性疾病，药物处方，以及心脏病发作，中风，肾衰竭和心力衰竭的最普遍的危险因素。 对降压药物治疗的反应表现出相当大的患者间差异，导致HTN控制率差。 我们建议确定遗传预测的抗高血压和不良代谢反应的两个首选和药效学对比的药物，β-受体阻滞剂（阿替洛尔）和噻嗪类利尿剂（HCTZ）最初作为单药治疗，随后在组合，800个人与无并发症的高血压。 高质量的表型数据反应，脂质和胰岛素敏感性措施的不良代谢反应将通过两种方法与遗传变异。 首先，在70个候选基因中检测7个SNP，我们将研究这些基因变异对β受体阻滞剂和利尿剂反应的影响。这将包括评估与以下因素的遗传相关性：单药治疗的抗高血压反应、单药治疗中添加第二种药物、联合治疗以及单药和联合治疗的不良代谢反应。 这种候选基因方法将通过检测20，000个跨越人类基因组的推定功能SNP来发现参与可变BP和对β受体阻滞剂和利尿剂的代谢反应的新基因来补充。 这项研究将大大增加我们对单用和联合降压药物治疗的遗传药理学的理解。 这可能会导致更高的HTN控制率，减少对多种药物的需求，降低医疗保健成本，并改善结果。