Pharmacogenetic aspects of drug interactions in stroke patients (using the CYP2C9 gene as an example)

Abstract

Relevance. The safety of stroke pharmacotherapy against the background of polypharmacy is of paramount importance in modern clinical practice. Genetic polymorphisms of cytochrome P450 genes, including the CYP2C9 gene, significantly contribute to drug responses and drug-drug interactions. The alleles with reduced function are CYP2C9*2 (R144C, rs1799853) and CYP2C9*3 (I359L, rs1057910). Objective. Analysis of the frequency distribution of alleles and genotypes of the CYP2C9 gene (rs1057910, rs1799853) in stroke patients, taking into account possible drug interactions in real clinical practice in Arkhangelsk. Materials and methods. A cross-sectional study was conducted on a sample of patients diagnosed with stroke, hospitalized in the neurology department of the regional vascular center of the First City Clinical Hospital named after E. E. Volosevich of the Arkhangelsk Region. Patients were divided into two groups: those initially hospitalized and those readmitted. Polymorphic variants of the CYP2C9 gene were studied: rs1057910 (Ile359Leu), rs1799853 (Arg144Cys) by real-time polymerase chain reaction using a Bio-Rad CFX96 Touch amplifier. Results. The study included 81 patients aged 43 to 95 years with a diagnosed stroke. Statistically significant differences were observed in the blood potassium level of 4.2 (3,865–4,615) in the group with primary hospitalization and 4,575 (4.31–4,845) in the group with repeated hospitalization (р=0,022). Carriers of low-functional variants of the CYP2C9 gene were identified in both groups: Ile359Leu (rs1057910), Arg144Cys (rs1799853). Statistically significant differences between the CYP2C9 gene allele variants and the frequency of repeated hospitalizations are not detected (p>0.05). The analysis of pharmacotherapy in the study sample of post-stroke patients revealed potential undesirable drug interactions between clopidogrel and acetylsalicylic acid as a risk factor for side effects. Conclusion. The study conducted in real clinical practice demonstrates the importance of introducing pharmacogenetic testing in stroke patients from the perspective of identifying potential drug interactions.