Statin Muscle Toxicity and Genetic Risk Factors

Hydroxymethylglutaryl-CoA (HMG-CoA) reductase inhibitors (statins) can cause skeletal muscle toxicity; the risk of toxicity is elevated by drug interactions and pharmacogenetic factors that increase the concentration of statins in plasma.The genetic basis of statin-related muscle disorders is largely unknown.Statins are substrates for several membrane transporters that may mediate drug interactions.Potent inhibitors of cytochrome P450 (CYP450) especially CYP3A4, can significantly increase the plasma concentrations of the active forms of atorvastatin, lovastatin and simvastatin.Fluvastatin, which is metabolized by CYP2C9, is less prone to pharmacokinetic interactions, while pravastatin and rosuvastatin are not susceptible to any CYP inhibition.OATP1B1 can decrease the hepatic uptake of many statins, as well as the therapeutic index of these agents.Polymorphisms of CYP450 enzymes, SLCO1B1, ABCB1, and COQ2 gene, can induce statin intolerance.This review summarized the principal relations known between statin myotoxicity and genetic risk factors.