Hopewell Jemma C, Reith Christina, Armitage Jane
CTSU, Nuffield Department of Population Health, University of Oxford, Oxford, UK *Jemma C. Hopewell, Christina Reith and Jane Armitage contributed equally to the writing of this article.
Curr Opin Lipidol. 2014 Dec;25(6):438-45. doi: 10.1097/MOL.0000000000000125.
To examine the current evidence concerning the effects of genetic variation on statin-related low-density lipoprotein cholesterol reductions, clinical efficacy, and adverse events and the relevance for patient care.
Recent years have seen the emergence of large-scale genetic experiments, including genome-wide association studies and candidate gene studies, exploring the impact of common genetic variation on patient response to statins. These studies have built on previous smaller scale evidence, providing improved statistical power and enhanced ability to explore the genome. Current evidence suggests that common genetic variants do not alter low-density lipoprotein cholesterol response by more than a few percent, or materially alter the effect of statin on vascular risk reduction, and therefore that patients benefit from statins independent of common genetic variation. However, knowledge of SLCO1B1 genotypes is believed to have clinical utility for predicting myopathy risk and ensuring that statins are prescribed as safely as possible. Furthermore, new hypothesis-generating studies, such as those associating GATM with myopathy risk, offer potential insights for the future.
Common genetic variation does not appear to be an important determinant of statin response, with the exception of SLCO1B1 and risk of myopathy. Future studies will help to determine the impact of low-frequency and rare genetic variation on statin response.
探讨目前关于基因变异对他汀类药物相关的低密度脂蛋白胆固醇降低效果、临床疗效及不良事件的影响的证据,以及其与患者护理的相关性。
近年来出现了大规模基因实验,包括全基因组关联研究和候选基因研究,以探索常见基因变异对患者他汀类药物反应的影响。这些研究建立在以往较小规模证据的基础上,提供了更高的统计效力和更强的基因组探索能力。目前的证据表明,常见基因变异对低密度脂蛋白胆固醇反应的改变不超过几个百分点,也不会实质性改变他汀类药物对降低血管风险的作用,因此患者无论常见基因变异情况如何都能从他汀类药物中获益。然而,SLCO1B1基因型的知识被认为对预测肌病风险和确保他汀类药物尽可能安全地处方具有临床实用性。此外,新的产生假设的研究,如那些将GATM与肌病风险相关联的研究,为未来提供了潜在的见解。
除了SLCO1B1和肌病风险外,常见基因变异似乎不是他汀类药物反应的重要决定因素。未来的研究将有助于确定低频和罕见基因变异对他汀类药物反应的影响。