Взаємозв’язок поліморфізму генів CYP2C9, CYP4F2, VKORC1 з розвитком геморагічних ускладнень при терапії варфарином у хворих з фібриляцією передсердь: результати одноцентрового річного спостереження

Abstract

The aim – to evaluate the effectiveness and safety of warfarin therapy in patients with atrial fibrillation (AF) in the anticoagulation practice, the rate of CYP2C9, CYP4F2, VKORC1 genes polymorphism and their interrelation with hemorrhagic complications among Zaporizhzhia region residents. Material and methods. We studied 41 patients with AF (mean age – 68.2±1.2 years, men – 19, women – 22) enrolled in a 1-year out-patient observation in the anticoagulation practice of Zaporizhzhia State Medical University clinics. All patients were treated with warfarin. CYP2C9, CYP4F2, VKORC1 genes polymorphism was determined using polymerase chain reaction method. Results. During one year hemorrhagic complications (small bleedings) arose in 22 (53.66 %) patients with AF, receiving warfarin therapy. Bleedings were significantly more frequent in the group of patients with VKORC1 gene mutation: 69.5 % vs. 37.5 %, respectively (χ2=5.331; Р<0.05). It was found that the relative risk of bleeding under warfarin treatment in patients with VKORC1 gene mutation is 1.97 (95 % CI 1.039; 3.751; Р<0.05). Conclusions. VKORC1 polymorphism is associated with increased frequency of hemorrhagic complications in patients with AF taking warfarin, indicating the relevance of a personalized approach to the warfarin dose titration using pharmacogenetic testing. The aim – to evaluate the effectiveness and safety of warfarin therapy in patients with atrial fibrillation (AF) in the anticoagulation practice, the rate of CYP2C9, CYP4F2, VKORC1 genes polymorphism and their interrelation with hemorrhagic complications among Zaporizhzhia region residents. Material and methods. We studied 41 patients with AF (mean age – 68.2±1.2 years, men – 19, women – 22) enrolled in a 1-year out-patient observation in the anticoagulation practice of Zaporizhzhia State Medical University clinics. All patients were treated with warfarin. CYP2C9, CYP4F2, VKORC1 genes polymorphism was determined using polymerase chain reaction method. Results. During one year hemorrhagic complications (small bleedings) arose in 22 (53.66 %) patients with AF, receiving warfarin therapy. Bleedings were significantly more frequent in the group of patients with VKORC1 gene mutation: 69.5 % vs. 37.5 %, respectively (χ2=5.331; Р<0.05). It was found that the relative risk of bleeding under warfarin treatment in patients with VKORC1 gene mutation is 1.97 (95 % CI 1.039; 3.751; Р<0.05). Conclusions. VKORC1 polymorphism is associated with increased frequency of hemorrhagic complications in patients with AF taking warfarin, indicating the relevance of a personalized approach to the warfarin dose titration using pharmacogenetic testing.