Effect of polymorphisms in CYP3A4*22 (rs35599367) C>T, CYP3A5*3 (rs776746) A>G, ABCB1 (rs4148738) C>T and ABCB1 (rs1045642) C>T genes on apixaban anticoagulation: pilot study results

Abstract

Introduction. Apixaban is a direct oral anticoagulant prescribed for treatment and prevention of venous thromboembolism (VTE) and for prevention of stroke in patients with nonvalvular atrial fibrillation. Direct oral anticoagulants (DOACs) such as apixaban are rapidly replacing warfarin therapy due to improved efficacy and safety profile shown in clinical trials. However, anticoagulants can cause serious and adverse drug reactions (ADRs).Aim. Study of the effect of carriage of polymorphisms in CYP3A4*22 (rs35599367) C>T, CYP3A5*3 (rs776746) A>G, ABCB1 (rs4148738) C>T and ABCB1 (rs1045642) C>T genes on the change in prothrombin time (PT) and activated partial thromboplastin time (aPTT) in patients using apixaban.Materials and methods. A total of 36 patients were enrolled onto this prospective observational study. All patients received apixaban at doses in accordance with instructions on how to administer the drug. Atrial fibrillation was diagnosed in 26 patients, and secondary thrombotic complications in 23 patients. To perform pharmacogenetic tests and measure aPTT and PT parameters, venous blood samples from each patient were drawn on Days 4-5 after prescription of apixaban. The PharmGKB database was used to select candidate genes for the study. Genotyping was performed using the real-time polymerase chain reaction technique. Statistical analysis: data were analyzed by using IBM SPSS Statistics program, Version 23.0.Results. In our study, we assessed the effect of polymorphisms in ABCB1 (rs1045738) C>T, ABCB1 (rs4148642) C>T genes on the aPTT and PT parameters. No statistically significant associations were found.Conclusion. The differences between PT and APTT values in patients using apixaban in the groups with different polymorphisms in ABCB1 (rs1045738) C>T, ABCB1 (rs4148642) C>T gene were not statistically significant. Further studies are necessary to assess the effect of pharmacogenetics on the safety and efficacy profile of apixaban.