Original scientific paper
Association of Cyp2c9 Gene Polymorphism with Bleeding as a Complication of Warfarin Therapy
Elizabeta Topić
Mario Štefanović
Lada Zibar
Goran Samardžija
Sanja Balen
Aleksandar Včev
Dragoslav Domanović
Jure Mirat
Jerko Barbić
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.
Keywords
gene polymorphism; CYP2C9; warfarin; bleeding
Hrčak ID:
27204
URI
Publication date:
7.7.2008.
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