University of Alabama at Birmingham, Birmingham AL 55294-0022, USA.
Pharmacogenomics. 2009 Aug;10(8):1295-307. doi: 10.2217/pgs.09.61.
Hypertension is a common condition associated with increased cardiovascular morbidity and mortality. In the USA only approximately a third of those who are aware of their hypertensive status successfully control their blood pressure. One reason for this is the unpredictable response individuals have to treatment. Clinicians must often rely on empirical methods to match patients with effective drug treatment. Hypertension pharmacogenetics seeks to find genetic predictors of response to drugs that lower blood pressure and to translate this knowledge into clinical practice. To date, around 60 studies have investigated associations between genetic polymorphisms and response to antihypertensive drugs. Here we review 18 studies that have been published since 2005. While consonant findings that are insufficient for clinical translation remain the norm, some consistent findings are emerging with several gene-treatment combinations. Nonetheless, differences in study designs, variable methods for assessing pharmacologic exposures, heterogeneous phenotypes (that is, response variables and outcomes ranging from blood pressure to clinical outcomes) and small sample sizes coupled with a short duration of follow-up in many studies account for a large portion of these inconsistencies. Progress in the future will depend upon our ability to launch large studies using high-fidelity phenotyping with multiple drugs and multiple ethnic groups.
高血压是一种常见的疾病,与心血管发病率和死亡率的增加有关。在美国,只有大约三分之一的高血压患者成功地控制了他们的血压。造成这种情况的一个原因是个体对治疗的反应不可预测。临床医生必须经常依靠经验方法来为患者匹配有效的药物治疗。高血压药物遗传学旨在寻找降压药物反应的遗传预测因子,并将这一知识转化为临床实践。迄今为止,大约有 60 项研究调查了遗传多态性与降压药物反应之间的关系。在这里,我们回顾了自 2005 年以来发表的 18 项研究。虽然一致的发现还不足以进行临床转化,但随着一些基因-治疗组合的出现,一些一致的发现正在出现。然而,研究设计的差异、评估药物暴露的方法不同、表型的异质性(即从血压到临床结果的反应变量和结果)以及许多研究中样本量小加上随访时间短,这些都导致了这些不一致的很大一部分。未来的进展将取决于我们是否有能力使用多种药物和多个种族进行高保真表型分析的大型研究。