PHARMACOGENOMIC EVALUATION OF ANTIHYPERTENSIVE RESPONSES (PEAR)

抗高血压反应的药物基因组学评价（梨）

• 批准号: 7605494
• 负责人: Julie E. Johnson
• 金额: $ 9.95万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-12-23 至 2007-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7605494
• 关键词: Adherence; Adverse effects; Antihypertensive Agents; Atenolol; Blood Pressure; Candidate Disease Gene; Chronic Disease; Combined Modality Therapy; Computer Retrieval of Information on Scientific Projects Database; Contrast Media; Data; Diuretics; Dropout; Drug Prescriptions; Evaluation; Exhibits; Funding; Genes; Genetic; Genetic Variation; Grant; Health Care Costs; Heart failure; Home environment; 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 (currently 34% in the US), and frequent non-adherence and dropout from therapy. We propose to identify genetic predictors of the antihypertensive and adverse metabolic responses to two preferred and pharmacodynamically contrasting drugs, a -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, including both home and ambulatory measures of blood pressure (BP) response, and 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 -blockers and diuretics (Specific Aim 1). This will include assessment of genetic associations with: antihypertensive responses to monotherapy (Aim 1a), addition of a second drug to monotherapy (Aim 1b), and combination therapy (Aim 1c); and adverse metabolic responses to mono and combination therapy (Aim 1d). This candidate gene approach will be supplemented by discovery of novel genes involved in variable BP and metabolic responses to -blockers and diuretics through testing of 20,000 pututative functional SNPs that span the human genome (Specific Aim 2). As in Aim 1, Aim 2 will include testing for associations with antihypertensive and adverse metabolic responses to monotherapy and combination therapy. The proposed research will substantially increase our understanding of the pharmacogenetics of mono- and combination antihypertensive drug therapy. The proposed research is significant because genetically-targeted antihypertensive therapy could lead to dramatically higher response rates and fewer adverse effects than the usual trial-and-error approach. This would likely lead to higher rates of HTN control, less need for polypharmacy, reduced health care costs, and improved outcomes.

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