Transporter Pharmacogenetics and Statin Toxicity
Transporter Pharmacogenetics and Statin Toxicity
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DOI：
10.1038/clpt.2009.197
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发表时间：
2010-01-01
影响因子：
6.7
通讯作者：
Niemi, M.
中科院分区：
文献类型：
--
作者：
Niemi, M.
转运蛋白基因的多态性对他汀类药物的药代动力学有深远的影响。特别是，有机阴离子转运多肽1B1的常见遗传变异减少了许多他汀类药物的肝脏摄取，增加了他汀类药物诱导的肌病的风险。类似地，遗传受损的三磷酸腺苷（ATP）结合盒G2转运蛋白外排活性导致各种他汀类药物的全身暴露显著增加。重要的是，这些遗传多态性的影响取决于所使用的特定他汀类药物。这为降脂治疗的个体化提供了合理依据。
Polymorphisms in transporter genes can have profound effects on statin pharmacokinetics. In particular, a common genetic variant of organic anion-transporting polypeptide 1B1 reduces the hepatic uptake of many statins, increasing the risk of statin-induced myopathy. Similarly, genetically impaired adenosine triphosphate (ATP)-binding cassette G2 transporter efflux activity results in a marked increase in systemic exposure to various statins. Importantly, the effects of these genetic polymorphisms differ depending on the specific statin that is used. This provides a rational basis for the individualization of lipid-lowering therapy.