Carriage of CYP2C19 gene alleles and possible drug-drug interactions in patients with coronary artery disease

Aim. To analyse the frequencies of the CYP2C19 gene alleles and genotypes associated with the metabolism of antiplatelet agents in patients with coronary artery disease (CAD), considering potential drug-drug interactions in real clinical practice in Arkhangelsk.

Material and methods. The cross-sectional study was conducted at the Emergency Cardiology Department of the Regional Vascular Center of the E.E. Volosevich First City Clinical Hospital in Arkhangelsk. The study included 96 patients diagnosed with CAD (I20.0-I22.0 according to ICD-10). Patients were divided into two groups: those hospitalized for the first time and those readmitted. All patients underwent pharmacogenetic testing of polymorphic variants of the CYP2C19 gene. Genotyping of polymorphic variants of the CYP2C19 gene was performed using the polymerase chain reaction (PCR) method in real time. The analysis of allelic variants rs28399504, rs4244285, rs4986893 of the CYP2C19 gene was performed on a Bio-Rad CFX96 Touch amplifier using the SNP-Screen kits (Synthol LLC, RF).

Results. The study included 96 patients with CAD aged 39 to 100 years. The patients were divided into two groups: primarily hospitalised and patients readmitted for recurrent acute coronary syndrome. The groups were comparable in sex and age. Significant differences were observed for INR: 1.05 [1.00; 1.14] in the first group and 1.08 [1.03; 1.14] in the second group (p=0.04), as well as for treatment outcome – 4 fatal cases (10%) were noted in the second group, while all patients in the first group were discharged (p=0.016). In both groups, carriers of low-functional CYP2C19 variants (G681A, G636A), classified as intermediate or poor metabolisers, were identified in both groups, which may be significant for drug-drug interactions in CAD pharmacotherapy in clinical practice. The A1G variant was identified only in the first group (3,6% (n=2)). No statistically significant difference was found in the frequency of loss-of-function alleles between the groups or in the

frequency of readmissions during antiplatelet therapy. Analysis of therapy in patients carrying pathological alleles revealed potentially adverse drug-drug interactions, e.g., clopidogrel and omeprazole, manifested as reduced clopidogrel efficacy and an increased risk of gastrointestinal bleeding.

Conclusion. This study did not reveal a statistically significant association between the presence of mutant CYP2C19 gene alleles and the frequency of readmissions, but emphasized the importance of a comprehensive personalized approach to pharmacotherapy in CAD patients. Consideration of pharmacogenetic, clinical, and pharmacological factors may contribute to therapy optimization and improvement of CAD treatment outcomes. Further studies with larger samples (including population-based studies) are required for definitive conclusions.

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