Kitzmiller Joseph P, Mikulik Eduard B, Dauki Anees M, Murkherjee Chandrama, Luzum Jasmine A
Department of Biological Chemistry and Pharmacology, College of Medicine.
College of Pharmacy, The Ohio State University, Columbus, OH.
Pharmgenomics Pers Med. 2016 Oct 3;9:97-106. doi: 10.2147/PGPM.S86013. eCollection 2016.
Statins are a cornerstone of the pharmacologic treatment and prevention of atherosclerotic cardiovascular disease. Atherosclerotic disease is a predominant cause of mortality and morbidity worldwide. Statins are among the most commonly prescribed classes of medications, and their prescribing indications and target patient populations have been significantly expanded in the official guidelines recently published by the American and European expert panels. Adverse effects of statin pharmacotherapy, however, result in significant cost and morbidity and can lead to nonadherence and discontinuation of therapy. Statin-associated muscle symptoms occur in ~10% of patients on statins and constitute the most commonly reported adverse effect associated with statin pharmacotherapy. Substantial clinical and nonclinical research effort has been dedicated to determining whether genetics can provide meaningful insight regarding an individual patient's risk of statin adverse effects. This contemporary review of the relevant clinical research on polymorphisms in several key genes that affect statin pharmacokinetics (eg, transporters and metabolizing enzymes), statin efficacy (eg, drug targets and pathways), and end-organ toxicity (eg, myopathy pathways) highlights several promising pharmacogenomic candidates. However, 521C is currently the only clinically relevant pharmacogenetic test regarding statin toxicity, and its relevance is limited to simvastatin myopathy.
他汀类药物是动脉粥样硬化性心血管疾病药物治疗和预防的基石。动脉粥样硬化性疾病是全球主要的死亡和发病原因。他汀类药物是最常用的处方药类别之一，在美国和欧洲专家小组最近发布的官方指南中，其处方适应症和目标患者群体已显著扩大。然而，他汀类药物治疗的不良反应会导致巨大的成本和发病率，并可能导致治疗中断。服用他汀类药物的患者中约10%会出现他汀类药物相关的肌肉症状，这是与他汀类药物治疗相关的最常见不良反应。大量的临床和非临床研究致力于确定遗传学是否能为个体患者他汀类药物不良反应的风险提供有意义的见解。这篇对影响他汀类药物药代动力学（如转运体和代谢酶）、他汀类药物疗效（如药物靶点和途径）以及终末器官毒性（如肌病途径）的几个关键基因多态性相关临床研究的当代综述突出了几个有前景的药物基因组学候选基因。然而，目前521C是唯一关于他汀类药物毒性的临床相关药物遗传学检测，其相关性仅限于辛伐他汀引起的肌病。
