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[他汀类药物诱导的横纹肌溶解症的遗传标志物]

[Genetic marker of statin-induced rhabdomyolysis].

作者信息

Chiba Kan, Morimoto Kaori

机构信息

Laboratory of Pharmacology and Toxicology, Graduate School of Pharmaceutical Sciences, Chiba University.

出版信息

Yakugaku Zasshi. 2011 Feb;131(2):247-53. doi: 10.1248/yakushi.131.247.

Abstract

This review summarizes genetic factors predisposed to statin-induced rhabdomyolysis. The first genetic risk factor of statin myopathy uncovered by genome-wide analysis of single nucleotide polymorphisms was the common variant of SLCO1B1 gene. Analysis of 30000 genetic markers in 85 patients with myopathy induced by high-dose simvastatin showed a strong association with 521T>C polymorphism of SLCO1B1. Another study also showed that this variant of SLCO1B1 has a significant association with myopathy in patients taking pravastatin or atorvastatin although the number of patients analyzed was limited. In addition to SLCO1B1, recent studies suggested that variants of genes encoding transporters (ABCG2 and ABCB1) and metabolic enzymes (CYP2C8 and UGT1A3) involved in the disposition of statins, and those involved in the metabolic muscle disease (glycogen storage disorders, carnitine palmitoyl-2 deficiency and myoadenylate deaminase deficiency) are also risk factors of statin-induced myopathy. These genetic factors may provide predisposition testing for statin-induced rhabdomyolysis.

摘要

本综述总结了易患他汀类药物诱导的横纹肌溶解症的遗传因素。通过对单核苷酸多态性进行全基因组分析发现的首个他汀类药物肌病遗传风险因素是SLCO1B1基因的常见变异。对85例高剂量辛伐他汀所致肌病患者的30000个遗传标记进行分析,结果显示其与SLCO1B1基因的521T>C多态性密切相关。另一项研究也表明,尽管分析的患者数量有限,但SLCO1B1基因的这一变异与服用普伐他汀或阿托伐他汀的患者的肌病显著相关。除了SLCO1B1基因外,最近的研究表明,参与他汀类药物处置的转运蛋白(ABCG2和ABCB1)和代谢酶(CYP2C8和UGT1A3)编码基因的变异,以及参与代谢性肌肉疾病(糖原贮积病、肉碱棕榈酰转移酶2缺乏症和肌腺苷酸脱氨酶缺乏症)的基因变异也是他汀类药物诱导肌病的风险因素。这些遗传因素可为他汀类药物诱导的横纹肌溶解症提供易感性检测。

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