Pharmacogenomics of antihypertensive drugs: rationale and design of the Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR) study.
Pharmacogenomics of antihypertensive drugs: rationale and design of the Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR) study.
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DOI：
10.1016/j.ahj.2008.11.018
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发表时间：
2009-03
影响因子：
4.8
通讯作者：
Turner, Stephen T.
中科院分区：
文献类型：
--
作者：
Johnson, Julie A.;Boerwinkle, Eric;Zineh, Issain;Chapman, Arlene B.;Bailey, Kent;Cooper-DeHoff, Rhonda M.;Gums, John;Curry, R. Whit;Gong, Yan;Beitelshees, Amber L.;Schwartz, Gary;Turner, Stephen T.
抗高血压治疗的选择通常是经验性的，利用遗传信息指导药物治疗的选择具有未来的希望。本试验的目的是确定对噻嗪类利尿剂（氢氯噻嗪，HCTZ）、β受体阻滞剂（阿替洛尔）及其联合用药的抗高血压和不良代谢反应的遗传决定因素。这将通过候选基因和全基因组关联方法来实现。招募年龄为17岁和65岁的无并发症高血压患者（n=800）。停止当前抗高血压治疗，沿着收集其他基线数据，确认高血压。然后将受试者随机分配至HCTZ或阿替洛尔组，采用一个剂量滴定步骤，然后在目标剂量至少6周后评估对治疗的反应。血压> 120/70 mmHg的患者增加第二种药物，剂量滴定和反应评估程序相似。收集的数据包括家庭、办公室和24小时动态血压。在禁食状态下收集的生物样品包括血浆、血清、DNA（血沉棕黄层）和尿液。也正在建立爱泼斯坦巴尔病毒转化的淋巴细胞系。药物遗传学指导治疗高血压具有临床潜力，但该领域的文献有限。这项试验将大大增加我们对两种常用降压药物的降压和不良代谢反应的遗传决定因素的理解。
Selection of antihypertensive therapy is often empiric and use of genetic information to guide drug therapy selection holds future promise. The objective of this trial is to identify the genetic determinants of the antihypertensive and adverse metabolic responses to a thiazide diuretic (hydrochlorothiazide, HCTZ), a β-blocker (atenolol) and their combination. This will be accomplished through candidate gene and genome wide association approaches. Individuals with uncomplicated hypertension (n=800), ages 17 and 65 years, are being enrolled. Current antihypertensive therapy is discontinued and hypertension is confirmed, along with collection of other baseline data. Subjects are then randomized to either HCTZ or atenolol, with one dose titration step, followed by assessment of response to therapy after at least 6 weeks on the target dose. Those with blood pressure > 120/70 mmHg have the second drug added, with similar dose titration and response assessment procedures. Data collected include home, office and 24 hour ambulatory blood pressure. Biological samples collected in the fasting state include plasma, serum, DNA (buffy coat), and urine. Epstein Barr virus transformed lymphocyte cell lines are also being created. Pharmacogenetic-guided therapy holds clinical potential for hypertension, but the literature in the field is limited. This trial will add substantially to our understanding of the genetic determinants of antihypertensive and adverse metabolic responses to two commonly used antihypertensive drug classes.
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