他汀类药物代谢相关基因多态性与疗效和安全性的关联

他汀类药物是目前最有效的降低LDL-C水平从而降低心血管疾病风险的药物。但是,不同个体对不同他汀类药物的反应不同;导致差异的关键因素是他汀类药物在肝脏代谢和转运的遗传特性不同。特别是参与他汀类药物肝脏代谢的关键性转运蛋白如阴离子转运多肽(OATP1B1)(由SLCO1B1基因编码)以及乳腺癌抑制蛋白(BCRP)的基因多态性可影响他汀类药物的血浆及肝脏浓度,从而影响他汀类药物的疗效和安全性。他汀类药物在肌病风险或在降LDL-C的能力方面如发生变化,均会改变这类药物临床应用时的效益风险比,而且还会影响以开发新治疗为目的临床试验中他汀类药物的应用。

Effect and safety of statins associated with the gene polymorphisms of drug metabolism

Statins are the most effective medications for lowering plasma cholesterol levels and reducing cardiovascular risk.Some studies demonstrate that there are variations in individuals responsing to different statins,and therefore,＂one size does not fit all＂.Key factors in these variations are the genetic determinations of statin metabolism and transport within the liver. In particular, the membrane transporters organic anion-transporting polypeptide（OATP）lB1 and breast cancer resistance protein（BCRP） have been shown to play an important role in plasma and hepatic exposure of statins.Changes in either the LDL-C lowering of statins or myopathy risk can shift the risk-to-benefit ratio for their clinical use and have implications for statin management in clinical trials during the development of novel therapeutics.