Department of Medicine, Centre for Heart Lung Innovation, University of British Columbia, St. Paul's Hospital, Rm 166 - 1081 Burrard St., Vancouver, British Columbia V6Z 1Y6, Canada.
Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
Cardiovasc Res. 2018 Jul 1;114(8):1073-1081. doi: 10.1093/cvr/cvy119.
Statin therapy reduces cardiovascular events in patients with, or at risk of, atherosclerotic cardiovascular disease. However, statins are underutilized in patients for whom they are indicated and are frequently discontinued. Discontinuation may be the result of statin-associated muscle symptoms (SAMS), which encompass a broad spectrum of clinical phenotypes from myalgia to severe myopathy. As with many adverse drug reactions (ADRs), inter-individual variability in susceptibility to SAMS is due, at least in part, to differences in host genetics. The genetic basis for SAMS has been investigated in candidate gene studies, genome-wide association studies, and, more recently, studies of multi-omic networks, including at the transcriptome level. In this article, we provide a systematic review of the pharmacogenetic basis of SAMS, focusing on how an understanding of the genetic and molecular determinants of SAMS can be considered in a personalized approach to reduce the incidence of this ADR, optimize statin adherence, and reduce the risk for cardiovascular events.
他汀类药物治疗可降低动脉粥样硬化性心血管疾病患者或有此疾病风险患者的心血管事件。然而，他汀类药物在适应证患者中的使用率较低，且常被停药。停药可能是他汀类药物相关肌肉症状（SAMS）的结果，其包含从肌肉痛到严重肌病的广泛临床表型谱。与许多药物不良反应（ADR）一样，SAMS 的易感性个体间差异至少部分归因于宿主遗传学的差异。已经在候选基因研究、全基因组关联研究中，以及最近在包括转录组水平的多组学网络研究中，对 SAMS 的遗传基础进行了研究。在本文中，我们对 SAMS 的药物遗传学基础进行了系统综述，重点介绍了如何在个体化方法中考虑 SAMS 的遗传和分子决定因素，以降低这种 ADR 的发生率、优化他汀类药物的依从性并降低心血管事件的风险。
