Department of Medical Genetics, Centre for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, British Columbia, Canada.
J Cardiovasc Pharmacol. 2011 Sep;58(3):228-39. doi: 10.1097/FJC.0b013e3182163b82.
Individual response to medication is highly variable. For many drugs, a substantial proportion of patients show suboptimal response at standard doses, whereas others experience adverse drug reactions (ADRs). Pharmacogenomics aims to identify genetic factors underlying this variability in drug response, providing solutions to improve drug efficacy and safety. We review recent advances in pharmacogenomics of cardiovascular drugs and cardiovascular ADRs, including warfarin, clopidogrel, β-blockers, renin-angiotensin-aldosterone system inhibitors, drug-induced long QT syndrome, and anthracycline-induced cardiotoxicity. We particularly focus on the applicability of pharmacogenomic findings to pediatric patients in whom developmental changes in body size and organ function may affect drug pharmacokinetics and pharmacodynamics. Solid evidence supports the importance of gene variants in CYP2C9 and VKORC1 for warfarin dosing and in CYP2C19 for clopidogrel response in adult patients. For the other cardiovascular drugs or cardiovascular ADRs, further studies are needed to replicate or clarify genetic associations before considering uptake of pharmacogenetic testing in clinical practice. With the exception of warfarin and anthracycline-induced cardiotoxicity, there is lack of pharmacogenomic studies on cardiovascular drug response or ADRs aimed specifically at children or adolescents. The first pediatric warfarin pharmacogenomic study indeed indicates differences from adults, pointing out the importance and need for pediatric-focused pharmacogenomic studies.
个体对药物的反应高度可变。对于许多药物，相当一部分患者在标准剂量下表现出不理想的反应，而其他患者则出现药物不良反应 (ADR)。药物基因组学旨在确定药物反应这种变异性的遗传因素，为提高药物疗效和安全性提供解决方案。我们综述了心血管药物和心血管 ADR 药物基因组学的最新进展，包括华法林、氯吡格雷、β-受体阻滞剂、肾素-血管紧张素-醛固酮系统抑制剂、药物诱导的长 QT 综合征和蒽环类药物诱导的心脏毒性。我们特别关注药物基因组学发现对儿科患者的适用性，因为儿童的身体大小和器官功能发育变化可能会影响药物的药代动力学和药效学。有确凿证据表明 CYP2C9 和 VKORC1 基因变异对华法林剂量和 CYP2C19 对氯吡格雷反应的重要性，这些证据支持 CYP2C9 和 VKORC1 基因变异在成年患者中的重要性。对于其他心血管药物或心血管 ADR，在考虑将药物基因组学检测纳入临床实践之前，需要进一步研究以复制或阐明遗传关联。除了华法林和蒽环类药物诱导的心脏毒性外，针对儿童或青少年的心血管药物反应或 ADR 的药物基因组学研究很少。第一项儿科华法林药物基因组学研究确实表明与成人存在差异，这表明需要进行以儿科为重点的药物基因组学研究。
