The relationship between CYP2C9 gene polymorphisms and upper gastrointestinal bleeding in patients who used warfarin.
OBJECTIVE
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 efficiency 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 significantly different in the group with bleeding (p less 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.


CONCLUSIONS
CYP2C9*2 and CYP2C9*3 polymorphisms were related to the increase of excessive anticoagulation and bleeding risk in the patients who used warfarin.
1Internal Medicine, Sivas State Hospital, Sivas, 2Department of Internal  Medicine, Gastroenterology, School of Medicine, Cumhuriyet University, Sivas, 3School of Medicine, Department of Internal  Medicine, Gaziosmanpasa University, Tokat, 4Department of Medical Genetic, School of Medicine, Canakkale Onsekiz Mart  University, Canakkale; Turkey.
Mahmut
M
Ucar
Hakan
H
Alagozlu
Safak
S
Sahin
Ozturk
O
Ozdemir
D000284:Administration, Oral; D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage / Q000009:adverse effects*; D015415:Biomarkers / Q000097:blood; D065729:Cytochrome P-450 CYP2C9 / Q000235:genetics*; D004334:Drug Administration Schedule; D016903:Drug Monitoring / Q000379:methods; D005260:Female; D006471:Gastrointestinal Hemorrhage / Q000139:chemically induced* / Q000235:genetics; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D013923:Thromboembolism / Q000188:drug therapy; D013997:Time Factors; D016896:Treatment Outcome; D014859:Warfarin / Q000008:administration & dosage / Q000009:adverse effects*
D000925:Anticoagulants; D015415:Biomarkers; D014859:Warfarin; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9