senior teacher Semey Medical University Semey, Kazakhstan
Background: Today, statins are the drugs of choice for the treatment of patients with cardiovascular diseases (CVD). Numerous large-scale studies indicate the ineffectiveness of statins, in the presence of high patient compliance. It is also worth noting the high incidence of adverse drug reactions (ADRs), among which the greatest danger to life is (rhabdomyolysis). The risk of developing adverse reactions has a number of predisposing factors, one of which is the mechanism that leads to a change in the pharmacokinetics of statins at the level of cytochrome P450 isoenzymes 3A4 and 3A5 . Single nucleotide substitutions, which are also called single nucleotide polymorphisms (SNPs) or single nucleotide variants (SNVs), have a great influence on the features of the function of cytochrome. For example, there is a variant CYP3A5*3 (A6986G, rs 776746) whose carriage slows down the work of the enzyme, prolonging the half-life of metabolized drugs.
Objectives: Еo study the prevalence of alleles and genotypes of cytochrome CYP3A5*3 (A6986G) in patients of the Kazakh population with coronary artery disease and dyslipidemia.
Methods:
Design: prospective cohort study. The study included 118 patients with coronary artery disease (having a very high risk of cardiovascular complications: after revascularization of the coronary arteries) with hypercholesterolemia. All patients were of Kazakh nationality aged 40 to 70 years. Before carrying out hypolipidemic statin therapy, patients, after DNA isolation, underwent genotyping of the CYP3A5 (A6986G) gene using real-time PCR SNP-EXPRESS – PB. Genetic studies were carried out on the basis of the PCR laboratory of the Semey State Medical University University Hospital.
Results: The average age of patients was 62.2±2.5 years, of which 77% were men. Of the concomitant diagnoses, 35.6% of patients suffered from type 2 diabetes mellitus, 95% had hypertension, a history of stroke - 23.8%, atrial fibrillation (AF) was indicated in 6% of patients and atherosclerosis of the vessels of the lower extremities-7.1%. 75 people had the AA genotype according to the allele variant CYP3A5 (A6986G) (63,6%), 29 (25,0 %) – genotype AG and 14 (11.4%) – genotype GG. Patients with allele A accounted for 76.1% and with allele G23.9%.
Conclusions: The prevalence of the polymorphic variant of the CYP3A5 gene (A6986G) among patients with coronary heart disease in the Kazakh population is 23.9%. The association between the carrier of genotypes for the polymorphic marker A6986G of the CYP3A5 gene and the drug response to statin therapy is the subject of further research.