The Influence of Genetic Polymorphisms on Warfarin Dosage Requirements in Cardiac Valve Surgery Patients

Abstract

Aim: Warfarin, a widely prescribed anticoagulant, exhibits considerable variability in patient response, making its clinical use challenging due to a narrow therapeutic window. This study aimed to evaluate the prevalence of CYP2C9 and VKORC1 gene polymorphisms in a cohort of 87 Turkish patients who underwent cardiac valve surgery and received warfarin therapy, as well as to assess their impact on warfarin dosage requirements. Methods: The frequencies of CYP2C9 and VKORC1 polymorphisms were analyzed, and patients were stratified based on the presence or absence of mutations affecting warfarin dosing. Results: Revealed that patients carrying at least one CYP2C9 or VKORC1 polymorphism required a significantly lower weekly warfarin dose to achieve the optimal international normalized ratio (INR). Conclusion: This study highlights the critical role of genetic factors in determining warfarin dosage and supports the integration of pharmacogenetic testing into clinical practice to personalize warfarin therapy. Such an approach has the potential to enhance treatment outcomes and minimize the risk of adverse events. Further research involving larger sample sizes and diverse patient populations is warranted to validate these findings and refine the current understanding of the genetic determinants of warfarin dosing.

Keywords

• Warfarin
• CYP2C9
• VKORC1
• genetic polymorphisms
• cardiac valve surgery
• Turkish population

Kalp Kapak Cerrahisi Hastalarında Genetik Polimorfizmlerin Warfarin Dozaj Gereksinimleri Üzerine Etkisi

Öz

Giriş: Yaygın olarak reçete edilen bir antikoagülan olan varfarin, hasta yanıtında önemli farklılıklar göstererek, dar terapötik pencere nedeniyle klinik kullanımını zorlaştırmaktadır. Bu çalışmanın amacı, kalp kapak ameliyatı geçiren ve warfarin tedavisi alan 87 Türk hastadan oluşan bir kohorttaki CYP2C9 ve VKORC1 gen polimorfizmlerinin prevalansını ve bunların warfarin dozaj gereksinimleri üzerindeki etkisini değerlendirmeyi amaçlamıştır. Gereç ve Yöntemler: CYP2C9 ve VKORC1 polimorfizmlerinin sıklıkları analiz edildi ve hastalar, warfarin dozunu etkileyen mutasyonların varlığı veya yokluğuna göre sınıflandırıldı. Bulgular: En az bir CYP2C9 veya VKORC1 polimorfizmi taşıyan hastaların, optimal uluslararası normalleştirilmiş orana (INR) ulaşmak için önemli ölçüde daha düşük haftalık warfarin dozuna ihtiyaç duyduğu ortaya çıktı. Sonuç: Bu çalışma, warfarin dozajının belirlenmesinde genetik faktörlerin kritik rolünü vurgulamakta ve varfarin tedavisini kişiselleştirmek için farmakogenetik testlerin klinik uygulamaya entegrasyonunu desteklemektedir. Böyle bir yaklaşımın tedavi sonuçlarını iyileştirme ve olumsuz olay riskini en aza indirme potansiyeli vardır. Bu bulguları doğrulamak ve varfarin dozajının genetik belirleyicilerine ilişkin mevcut anlayışı geliştirmek için daha büyük örneklem boyutlarını ve farklı hasta popülasyonlarını içeren daha fazla araştırma yapılması gerekmektedir.

Anahtar Kelimeler

• Varfarin
• CYP2C9
• VKORC1
• genetik polimorfizmler
• kalp kapak ameliyatı
• Türk popülasyonu

Kaynakça

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