Pharmacogenetics of HMG-CoA reductase inhibitors (statins): perspectives of individualized, genotype-based therapy

Abstract

Statins’ efficacy in coronary heart disease treatment is well known, but their effectiveness is a subject to substantial individual differences. Partially, it is explained by genetic polymorphism. Individual pharmacological response to statins might depend on genetic polymorphism of the proteins determining statins’ pharmacokinetics and their mechanism of action, as well as proteins involved into atherosclerosis pathogenesis. People with alleles of CYP2C9, CYP3A4, CYP2D6, MDR-1, ОАТР-С genes could demonstrate more prominent hypolipidemic effects and/or more adverse events, due to modified pharmakokinetics. HMGCR and CETP polymorphism of the genes coding principal «targets» for statins, might affect the latter’s effectiveness as well. Some proteins, involved into atherosclerosis pathogenesis (APO-E, ABCG5/G8, CYP7A1) have allele variants explaining different answers to statin treatment. To optimize long-term statin therapy, more studies on genetic polymorphism links to adverse cardiovascular events, are needed.

Keywords

• statins
• coronary heart disease
• genetic polymorphism
• atherosclerosis