GENETIC EPIDEMIOLOGY OF RESPONSES TO ANTIHYPERTENSIVES

抗高血压药反应的遗传流行病学

• 批准号: 6351480
• 负责人: STEPHEN T TURNER
• 金额: $ 46.11万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-02-01 至 2002-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6351480
• 关键词: African American; aldosterone; blood chemistry; caucasian American; chlorothiazide; clinical research; clinical trials; epidemiology; essential hypertension; gene expression; genetic markers; genetic polymorphism; genotype; human subject; human therapy evaluation; linkage disequilibriums; outcomes research; pharmacogenetics; pharmacokinetics; racial /ethnic difference; renin angiotensin system; statistics /biometry; urinalysis; African American; aldosterone; blood chemistry; caucasian American; chlorothiazide; clinical research; clinical trials; epidemiology; essential hypertension; gene expression; genetic markers; genetic polymorphism; genotype; human subject; human therapy evaluation; linkage disequilibriums; outcomes research; pharmacogenetics; pharmacokinetics; racial /ethnic difference; renin angiotensin system; statistics /biometry; urinalysis

DESCRIPTION: (Adapted from Investigator's Abstract) Essential hypertension is a common disorder that contributes to morbidity, mortality, and cost of health care, especially among African-Americans. although diuretics are commonly prescribed for treatment of hypertension, blood pressure decreases in response to diuretic therapy in some individuals but not in others. The proposed research will determine whether measured variation in genes coding for components of the renin-angiotensin-aldosterone (RAA) system predicts interindividual differences in blood pressure response to diuretic therapy in 300 hypertensive African-Americans and in 300 hypertensive non-Hispanic whites (total 600 individuals). The investigators will conduct a standardized clinical protocol in which hypertensive adults are treated with the diuretic hydrochlorothiazide, 25 mg/day, for four weeks. They will measure interindividual variation in five RAA system genes-- angiotensinogen, renin, angiotensin-1 converting enzyme, angiotensin-II receptor, and aldosterone synthase --to accomplish the following specific aims in each ethnic group. Aim 1: To determine whether variation in genes of the RAA system predicts interindividual differences in blood pressure response to diuretic therapy. Aim 2: To determine whether variation in genes of the RAA system predicts interindividual differences in baseline measures of the endocrine RAA system or response of these measures to diuretic therapy. Aim 3: To determine whether the predictive effects of variations in genes of the RAA system on blood pressure response to diuretic therapy detected in Aim 1 are mediated through their effects on baseline measures of the endocrine RAA system or response of these measures to diuretic therapy, detected in Aim 2. Results of the proposed research have the potential to identify genes contributing to the etiology of interindividual differences in blood pressure response to diuretic therapy in African-Americans and in non-Hispanic whites.

描述：（根据调查员的摘要改编）必需高血压 是一种常见疾病，有助于发病率，死亡率和成本 医疗保健，尤其是在非裔美国人中。 虽然利尿剂是 通常用于治疗高血压的规定，血压降低 为了回应某些人的利尿治疗，但在另一些人中没有。 这 拟议的研究将确定是否测量了基因编码的变化 对于肾素 - 血管紧张素 - 醛固酮（RAA）系统的组件预测 血压对利尿治疗的血压反应差异 在300名高血压非裔美国人和300名高血压非西班牙裔中 白人（总共600个人）。 调查人员将进行 标准化临床方案，其中高血压成年人接受治疗 利尿剂 氢氯噻嗪，25毫克/天，持续四个星期。 他们将衡量 五个RAA系统基因的个体变异 - 血管紧张素原，肾素，， 血管紧张素1转化酶，血管紧张素-II受体和醛固酮 合成酶 - 在每个种族中完成以下特定目标。 目标1：确定RAA系统基因的变化是否预测 血压对利尿治疗的血压反应差异。 目标2：确定RAA系统基因的变化是否预测 内分泌RAA系统基线测量的个体差异 或这些措施对利尿治疗的反应。 目标3：确定基因变异的预测效应是否 RAA系统的血压反应对利尿治疗中检测到的 AIM 1通过对基线测量的影响来介导 内分泌RAA系统或这些措施对利尿治疗的反应， 在AIM 2中检测到。 拟议研究的结果有可能识别基因 有助于血液间个体差异的病因 对非裔美国人的利尿治疗的压力反应 非西班牙裔白人。