Duke Institute for Genome Science & Policy, Duke University, Durham, NC 27708, USA.
J Am Coll Cardiol. 2012 Jul 3;60(1):9-20. doi: 10.1016/j.jacc.2012.01.067.
Pharmacogenetics primarily uses genetic variation to identify subgroups of patients who may respond differently to a certain medication. Since its first description, the field of pharmacogenetics has expanded to study a broad range of cardiovascular drugs and has become a mainstream research discipline. Three principle classes of pharmacogenetic markers have emerged: 1) pharmacokinetic; 2) pharmacodynamic; and 3) underlying disease mechanism. In the realm of cardiovascular pharmacogenetics, significant advances have identified markers in each class for a variety of therapeutics, some with a potential for improving patient outcomes. While ongoing clinical trials will determine if routine use of pharmacogenetic testing may be beneficial, the data today support pharmacogenetic testing for certain variants on an individualized, case-by-case basis. Our primary goal is to review the association data for the major pharmacogenetic variants associated with commonly used cardiovascular medications: antiplatelet agents, warfarin, statins, beta-blockers, diuretics, and antiarrhythmic drugs. In addition, we highlight which variants and in which contexts pharmacogenetic testing can be implemented by practicing clinicians. The pace of genetic discovery has outstripped the generation of the evidence justifying its clinical adoption. Until the evidentiary gaps are filled, however, clinicians may choose to target therapeutics to individual patients whose genetic background indicates that they stand to benefit the most from pharmacogenetic testing.
药物遗传学主要利用遗传变异来识别可能对特定药物反应不同的患者亚组。自首次描述以来，药物遗传学领域已经扩展到研究广泛的心血管药物，并已成为主流研究学科。已经出现了三类主要的药物遗传学标记：1）药代动力学；2）药效学；和 3）潜在疾病机制。在心血管药物遗传学领域，重大进展已经确定了各种治疗方法中每个类别的标记物，其中一些具有改善患者预后的潜力。虽然正在进行的临床试验将确定常规使用药物遗传学检测是否有益，但目前的数据支持针对特定变体的个体化、逐个病例的药物遗传学检测。我们的主要目标是回顾与常用心血管药物相关的主要药物遗传学变体的关联数据：抗血小板药物、华法林、他汀类药物、β受体阻滞剂、利尿剂和抗心律失常药物。此外，我们还强调了在哪些情况下可以由执业临床医生实施药物遗传学检测。遗传发现的速度已经超过了证明其临床应用的证据的产生。然而，在填补证据空白之前，临床医生可能会选择针对那些遗传背景表明他们最有可能从药物遗传学检测中受益的个体患者的治疗方法。
