Association of CYP2C9 gene polymorphism with bleeding as a complication of warfarin therapy.

Abstract

The aim of this study was to determine the association of bleeding as a complication of warfarin therapy with polymorphism of CYP2C9 gene (alleles 1, 2 and 3). The CYP2C9 is the main enzyme for warfarin metabolism. Study included 181 patients receiving warfarin for at least one month. Allele 1 of CYP2C9 gene (in 94.5%) and genotype *1/*1 (57.5%) prevailed. Allele 3 was found in 12.7% patients. Bleeding side-effects occurred in 18 patients (10%). Patients with allele *1 needed significantly higher maintenance warfarin dose (p=0.011). Those with allele *3 had significantly lower maintenance warfarin dose (p=0.005) and higher prothrombin time (PT) at induction (p=0.034). Bleeding occurred significantly more often in those with lower maintenance warfarin dose (p=0.017). Patients with allele *3 had increased risk of bleeding, with marginal significance (p=0.05). Polymorphism of CYP2C9 could determine dose of warfarin therapy and thus it could be related to the risk of bleeding complications. Allele *3 carriers need lower warfarin dose. Therefore, initially reduced warfarin induction dose in allele *3 carriers could avoid more prolonged PT and decrease the risk of bleeding complication.