THE ROLE OF PHARMACOGENOMIC STUDIES IN INCREASING THE EFFECTIVENESS AND SAFETY OF CLINICAL APPLICATION OF STATINS

Abstract

Introduction. Currently, hydroxymethylglutaryl-coenzyme A reductase inhibitors (statins) are among the most widely used hypolipidemic drugs worldwide. However, to date, the problems of the insufficient effectiveness of statin therapy and the development of unwanted side effects in patients remain not fully resolved. The identification of key variants in genes whose protein products are involved in statin metabolism and their effect on carriers during therapy may improve the efficacy of statin treatment and help prevent unwanted side effects, and therefore may be a valuable tool for clinicians when monitoring the progress of patients. to whom these medicines were prescribed. Aim. To summarize the information available in the literature on variants in genes that affect the effectiveness and safety of statins during treatment. Materials and methods. An assessment of the current literature on the role of genetic variants in the effectiveness and safety of statins was made. The search was performed in Scopus, Web of Science, Google Scholar, and PubMed databases. Results. The chemical structure and metabolism of statins are described. A review of the current literature on the impact of variants in ABCB1, ABCG2, CYP3A4, CYP3A5, and SLCO1B1 genes on the effectiveness of statin therapy and the development of unwanted side effects in patients is presented. These genes have been shown to be associated with the pharmacodynamics and pharmacokinetics of statins, which affect their efficacy and safe use. Conclusions. Since recent studies have demonstrated the influence of protein transporters such as ABCB1, ABCG2, OATP and BCRP, as well as the cytochrome P450 system, on the pharmacokinetics and pharmacodynamics of statins, further large-scale studies focusing on drug transporters are needed. The review focused on finding correlations between polymorphic variants in the genes encoding the aforementioned transporters and CYP enzymes and the efficacy and safety of statins. The presented data of the literature emphasize the importance of pharmacogenetic studies of statins, which can be useful to clinicians to minimize the negative consequences of taking these drugs and improve the effectiveness of treatment of patients who are carriers of risk alleles.