Genetic factors affecting statin concentrations and subsequent myopathy: a HuGENet systematic review.
Genetic factors affecting statin concentrations and subsequent myopathy: a HuGENet systematic review.
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DOI：
10.1038/gim.2014.41
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发表时间：
2014-11
期刊：
影响因子：
--
通讯作者：
Thummel KE
中科院分区：
文献类型：
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作者：
Canestaro WJ;Austin MA;Thummel KE
他汀类药物，3-羟基-3-甲基-戊二酰辅酶A还原酶抑制剂，已被证明在降低低密度脂蛋白水平和预防主要冠状动脉事件方面都有功效，使其成为美国最常用的处方药之一。他汀类药物具有肌肉毒性和虚弱的副作用，这导致监管机构对其实施剂量限制和召回。本综述的重点是与他汀类药物肌肉浓度增加相关的最具特征的遗传因素，包括编码细胞色素P450酶（CYP2D6、CYP3A4和CYP3A5）、线粒体酶（GATM）、内流转运蛋白（SLCO1B1）和外流转运蛋白（ABCB1和ABCG2）的基因。我们进行了一项系统的文献综述，以确定评估遗传变异对他汀类药物浓度改变和随后的他汀类药物相关肌病的预测意义的相关研究。有资格纳入的研究必须包含基因型信息，并且必须将其与肌病的某些测量相关联，无论是肌酸激酶水平还是自我报告的肌肉疼痛。在初步审查之后，重点放在七个充分表征的基因上，以提供实质性的审查：CYP2D6， CYP3A4, CYP3A5， GATM, SLCO1B1， ABCB1和ABCG2。所有他汀类药物均纳入本综述。在评估的遗传因素中，他汀类药物相关肌病似乎与SLCO1B1的变异最密切相关。
Statins, 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitors, have proven efficacy in both lowering low-density-lipoprotein levels and preventing major coronary events, making them one of the most commonly prescribed drugs in the United States. Statins exhibit a class-wide side effect of muscle toxicity and weakness, which has led regulators to impose both dosage limitations and a recall. This review focuses on the best-characterized genetic factors associated with increased statin muscle concentrations, including the genes encoding cytochrome P450 enzymes (CYP2D6, CYP3A4, and CYP3A5), a mitochondrial enzyme (GATM), an influx transporter (SLCO1B1), and efflux transporters (ABCB1 and ABCG2). A systematic literature review was conducted to identify relevant research evaluating the significance of genetic variants predictive of altered statin concentrations and subsequent statin-related myopathy. Studies eligible for inclusion must have incorporated genotype information and must have associated it with some measure of myopathy, either creatine kinase levels or self-reported muscle aches and pains. After an initial review, focus was placed on seven genes that were adequately characterized to provide a substantive review: CYP2D6, CYP3A4, CYP3A5, GATM, SLCO1B1, ABCB1, and ABCG2. All statins were included in this review. Among the genetic factors evaluated, statin-related myopathy appears to be most strongly associated with variants in SLCO1B1.