1] The Wolfson Centre for Personalised Medicine, Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK [2] Clinical Pharmacology, The Royal Liverpool University Hospital, Liverpool, UK.
Clin Pharmacol Ther. 2014 Mar;95(3):281-93. doi: 10.1038/clpt.2013.234. Epub 2013 Dec 9.
Cardiovascular disease is a leading cause of morbidity and mortality worldwide. Pharmacogenomics is the study of genetic determinants of interindividual variation in drug response and aims to facilitate personalized medicine, through genotype-informed drug and dose selection, to maximize drug efficacy and/or minimize adverse drug reactions. Despite high expectations, no cardiovascular pharmacogenomic association is currently in widespread clinical practice; evidential, logistical, financial, and knowledge implementation barriers exist. Nevertheless, VKORC1, CYP2C9, and CYP4F2 variants have been associated with warfarin dose requirements, and CYP2C19 variants have been associated with perturbed antiplatelet response to clopidogrel. However, at present, controversy exists over the clinical utility of these genetic associations. There is an increased risk of simvastatin-induced muscle toxicity in SLCO1B1*5 carriers, ADRB1 and ADRA2C polymorphisms are associated with differential response to bucindolol, and rare congenital arrhythmia gene variants have been identified in drug-induced torsade de pointes. Practical benefits are still anticipated, but much work remains.
心血管疾病是全球发病率和死亡率的主要原因。药物基因组学是研究药物反应个体间差异的遗传决定因素，旨在通过基因型指导的药物和剂量选择促进个体化医学，以最大限度地提高药物疗效和/或最小化药物不良反应。尽管期望很高，但目前没有心血管药物基因组学关联在广泛的临床实践中得到应用；存在证据、后勤、财务和知识实施方面的障碍。然而，VKORC1、CYP2C9 和 CYP4F2 变体与华法林剂量需求相关，CYP2C19 变体与氯吡格雷抗血小板反应失调相关。然而，目前，这些遗传关联的临床实用性存在争议。SLCO1B1*5 携带者使用辛伐他汀会增加肌肉毒性的风险，ADRB1 和 ADRA2C 多态性与布新洛尔的反应差异相关，药物诱导的尖端扭转型室性心动过速中已发现罕见的先天性心律失常基因变异。预计仍将带来实际效益，但仍有很多工作要做。
