Center for Pharmacogenomics, Department of Pharmacotherapy and Translational Research, University of Florida, Box 100486, Gainesville, FL 32610-0486, USA.
Pharmacol Rev. 2013 May 17;65(3):987-1009. doi: 10.1124/pr.112.007252. Print 2013 Jul.
The past decade has seen tremendous advances in our understanding of the genetic factors influencing response to a variety of drugs, including those targeted at treatment of cardiovascular diseases. In the case of clopidogrel, warfarin, and statins, the literature has become sufficiently strong that guidelines are now available describing the use of genetic information to guide treatment with these therapies, and some health centers are using this information in the care of their patients. There are many challenges in moving from research data to translation to practice; we discuss some of these barriers and the approaches some health systems are taking to overcome them. The body of literature that has led to the clinical implementation of CYP2C19 genotyping for clopidogrel, VKORC1, CYP2C9; and CYP4F2 for warfarin; and SLCO1B1 for statins is comprehensively described. We also provide clarity for other genes that have been extensively studied relative to these drugs, but for which the data are conflicting. Finally, we comment briefly on pharmacogenetics of other cardiovascular drugs and highlight β-blockers as the drug class with strong data that has not yet seen clinical implementation. It is anticipated that genetic information will increasingly be available on patients, and it is important to identify those examples where the evidence is sufficiently robust and predictive to use genetic information to guide clinical decisions. The review herein provides several examples of the accumulation of evidence and eventual clinical translation in cardiovascular pharmacogenetics.
在过去的十年中,我们对影响各种药物反应的遗传因素的理解取得了巨大进展,包括那些针对心血管疾病治疗的药物。在氯吡格雷、华法林和他汀类药物的情况下,相关文献已经足够强大,现在已经有指南描述了如何利用遗传信息来指导这些治疗方法的应用,一些医疗中心正在将这些信息应用于患者的治疗中。从研究数据转化为实际应用存在许多挑战;我们讨论了其中的一些障碍,以及一些医疗系统正在采取的方法来克服这些障碍。本文全面描述了导致 CYP2C19 基因分型用于氯吡格雷、VKORC1、CYP2C9 和 CYP4F2 用于华法林以及 SLCO1B1 用于他汀类药物的临床实施的文献。我们还为其他与这些药物相关但数据存在争议的基因提供了更清晰的认识。最后,我们简要评论了其他心血管药物的药物遗传学,并强调了β受体阻滞剂作为具有强大数据但尚未见临床应用的药物类别。预计患者的遗传信息将越来越多,因此,重要的是要确定那些证据足够强大且具有预测性的例子,以便利用遗传信息来指导临床决策。本文提供了心血管药物遗传学中证据积累和最终临床转化的几个例子。