Pharmacogenetic Approaches to Enhancing Efficacy and Safety of Statins as Illustrated by the Example of Atorvastatin

Abstract

Statins are efficacious lipid-lowering drugs used for prevention of cardiovascular complications in patients with high blood cholesterol. The efficacy and safety of this group of drugs is largely determined by genetic factors. The aim of the study was to analyse the effect of gene polymorphisms on the efficacy and safety of atorvastatin in patients undergoing hospital treatment. Materials and methods. The authors carried out a retrospective study of the medical records of 76 hospital patients who were prescribed atorvastatin for confirmed hyperlipidemia. All the patient records contained the results of genotyping of single nucleotide polymorphisms that presumably affect the pharmacokinetics and pharmacodynamics of statins. Results. The analysis of literature data suggested that the pharmacological response and safety of statins could be affected by polymorphisms of the following genes: SLCO1B1 , ABCB1 , CYP2C9 , and CYP2C19 . The study showed that atorvastatin had high efficacy in the carriers of the 3435C allele of the ABCB1 gene and in the carriers of the CYP2C19*2 allele of the CYP2C19 gene. The patients carrying ABCB1 genotypes demonstrated a tendency to increasing levels of low-density lipoproteins and total cholesterol in the following order: 3435 СС → 3435 СТ → 3435 ТТ . The only adverse reaction of atorvastatin in the patient groups was an increase in the activity of hepatic transaminases, however, no connection with the studied gene polymorphisms was observed. Conclusions. The study of the effect of gene polymorphisms on the efficacy and safety of statins will be continued to obtain statistically valid confirmation of the observed trends in a much larger group of patients.