Comprehensive assessment of variants of cytochrome system, APOE and SLCO1B1 genes, potentially affecting the action of statins

E. V. Zyatenkova; A. I. Ershova; A. N. Meshkov; A. V. Kiseleva; O. P. Skirko; M. V. Klimushina; A. V. Blokhina; M. S. Pokrovskaya; O. M. Drapkina

doi:10.25557/2073-7998.2020.05.71-73

Comprehensive assessment of variants of cytochrome system, APOE and SLCO1B1 genes, potentially affecting the action of statins

E. V. Zyatenkova, A. I. Ershova, A. N. Meshkov, A. V. Kiseleva, O. P. Skirko, M. V. Klimushina, A. V. Blokhina, M. S. Pokrovskaya, O. M. Drapkina

https://doi.org/10.25557/2073-7998.2020.05.71-73

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Abstract

Variants of genes in the cytochrome P 450 system and carrier proteins play a role in changing the pharmacokinetics and pharmacodynamics of statins, which can lead to a decrease in the effectiveness of drug therapy and the development of undesirable drug reactions. Aim: to evaluate combinations of SNPs of the CYP3A4, CYP3A5, CYP2C9, CYP2C19, CYP2D6, APOE, SLCO1B1 genes that potentially affect the action of statins in a random sample of patients. In 38 randomly selected patients, 60 SNP were examined using real-time polymerase chain reaction and TaqMan® OpenArray® PGx (ThermoFisherScientific, США). All patients had at least one SNP associated with the effectiveness of statins. In 39%, combinations of at least two SNPs have been identified that potentially affect the action of statins. In 25% of patients, combinations of CYP2C19 (rs4244285, rs12248560 or rs4986893) and CYP2C9 (rs28371688 or rs1799853) variants were revealed. 13% patients had combinations of CYP3A4 (rs55785340 or rs2740574), CYP3A5 (rs77676746), and CYP2D6 (rs5030656, rs1065852, rs28371725 or rs3892097) variants. All variants except rs776746 were heterozygous. In 29% of patients, APOE SNPs were detected. 25% of patients had the CT genotype rs4149056 of the SLCO1B1 gene. The proportion of patients with CT genotype rs4149056 and at least two SNPs genes associated with statin efficacy was 45%. Due to the high prevalence of SNP genes involved in statin metabolism, as well as the insignificant effect of SNP alone, according to the literature, it can be assumed that in order to increase the informativeness of pharmacogenetic testing in statin therapy, it is necessary to study the effect of not individual SNPs, but their combinations.