The relationship between CYP2C9 gene polymorphisms and upper gastrointestinal bleeding in patients who used warfarin

Abstract

Aim Oral anticoagulants are the most common used substance for treatment and prophylaxis of warfarin venous and arterial thromboembolic disorders in the world. Therapeutic index of warfarin is narrow. CYP2C9 is a hepatic microsomal enzyme and has a primary role in metabolism of warfarin and genetic variations of CYP2C9 may cause a serious effect on the response to warfarin in patients. The aim of this study was to determine the eficiency of CYP2C9 gene polymorphisms on drug metabolism in patients who had upper gastrointestinal system bleeding while using warfarin. Methods There was a total of 67 patients in this study, 37 of whom had upper gastrointestinal system bleeding when INR was above 3 while using warfarin (group 1), 30 of whom had no bleeding and INR was stable under 3 (group 2). Results There was no difference in terms of warfarin dose used among the groups (p>0.05). Mutant genotype, INR and aspirin usage were found signiicantly different in the group with bleeding (p<0.05). When analyzed in terms of drug interaction, there was no difference between the two groups (p>0.05). Logistic regression analysis was made in order to determine the risk factors that may cause bleeding. Aspirin usage (p= 0.016) and genetic polymorphism (p= 0.024) were related to the increased risk of bleeding. Conclusion CYP2C9*2 and CYP2C9*3 polymorphisms were related to the increase of excessive anticoagulation and bleeding risk in the patients who used warfarin.