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心血管药物基因组学:当前知识状况及实际应用

Cardiovascular pharmacogenomics; state of current knowledge and implementation in practice.

作者信息

Shahabi Payman, Dubé Marie-Pierre

机构信息

Beaulieu-Saucier Pharmacogenomics Centre, Montreal Heart Institute, Montreal, Quebec, Canada; Department of Medicine and Social and Preventive Medicine, University of Montreal, Montreal, Quebec, Canada.

出版信息

Int J Cardiol. 2015 Apr 1;184:772-795. doi: 10.1016/j.ijcard.2015.02.025. Epub 2015 Feb 25.

Abstract

Pharmacogenomics (PGx) is the science that examines how an individual's genetic make-up affects the safety and efficacy of therapeutic drugs. PGx of response to cardiovascular (CV) medications is of the most successfully translated branches of PGx into the clinical workout. However, the clinical implementation of PGx of CV drugs is yet far beyond the growth of our understanding of the role of genetics in drug therapy. A considerable amount of efforts have been devoted by the regulatory agents like the food and drug administration (FDA) as well as the expert-based networks such as the Clinical Pharmacogenetics Implementation Consortium (CPIC) to overcome the existing barriers. This has been done, at least in part, for some of the most widely prescribed CV drugs, including clopidogrel, warfarin and simvastatin for which the PGx knowledge have been satisfactorily robust to provoke the CPIC to issue the guidelines for these drugs and the FDA to update the drugs' labeling, both strongly recommended the use of genotype-guided dosing for these medications, provided that the genetic data are available. For other drugs, however, studies have produced contradictory results and further large and well-designed clinical trials are required to expand and confirm the clinical utility of their PGx data. This review paper presents the current state of knowledge in the field of PGx of CV medications and describes the facilities assisting to the translation of PGx data into the clinical practice. Afterward, the existing body of PGx literature of the most-commonly used CV medications is comprehensively discussed.

摘要

药物基因组学(PGx)是一门研究个体基因构成如何影响治疗药物安全性和有效性的科学。心血管(CV)药物反应的PGx是PGx领域中最成功地转化为临床应用的分支之一。然而,CV药物PGx的临床应用仍远远落后于我们对遗传学在药物治疗中作用的理解的发展。食品药品监督管理局(FDA)等监管机构以及临床药物基因组学实施联盟(CPIC)等基于专家的网络已经投入了大量努力来克服现有障碍。至少在一定程度上,对于一些最常用的CV药物,包括氯吡格雷、华法林和辛伐他汀,其PGx知识已经足够完善,促使CPIC发布这些药物的指南,FDA更新这些药物的标签,两者都强烈建议在有基因数据的情况下,对这些药物采用基因型指导给药。然而,对于其他药物,研究结果相互矛盾,需要进一步开展大规模、设计良好的临床试验来扩大和确认其PGx数据的临床实用性。本文综述了CV药物PGx领域的当前知识状态,并描述了有助于将PGx数据转化为临床实践的工具。随后,对最常用CV药物的现有PGx文献进行了全面讨论。

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