The effect of CYP2C9 and VKORC1 genetic polymorphisms on warfarin dose requirements in a pediatric populationBirce Dilge Taşkın1, Serdar Kula2, Mehmet Ali Ergün3, Demet Altun5, Rana Olguntürk2, Fatma Sedef Tunaoğlu2, Ayşe Deniz Oğuz2, Türkiz Gürsel4
1Department of Pediatric Neurology, Ankara Childrens Hematology Oncology Training and Research Hospital, Ankara-Turkey
2Department of 1Pediatric Cardiology, Faculty of Medicine, Gazi University, Ankara-Turkey
3Medical Genetics, Faculty of Medicine, Gazi University, Ankara-Turkey
4Pediatric Hematology, Faculty of Medicine, Gazi University, Ankara-Turkey
5Department of Pediatrics, Etimesgut Air Force Hospital, Ankara-Turkey
Objective: The aim was to investigate the frequency of genetic polymorphisms of cytochrome P4502C9 (CYP2C9) and vitamin K epoxide reductase complex subunit1 (VKORC1) and determine the effect of these polymorphisms on warfarin dose requirements in pediatric patients.Keywords: CYP2C9, genetic polymorphism, INR, pharmacogenetics, VKORC1, warfarin
Methods: Fifty-eight pediatric patients with cardiac disease, thrombophilia, or other conditions, taking a stable warfarin dose, aged 0.218 years, and with international normalized ratio (INR) between 2 and 3 and 149 healthy children as a control group were included in this prospective, observational study. Patients receiving drugs that interact with warfarin, having chronic liver or renal disease, obesity, or thyroid dysfunctions were excluded. Polymerase chain reaction (real time and restriction fragment length polymorphism) was used to analyze the CYP2C9*2, CYP2C9*3, and VKORC1 polymorphisms. The ideal warfarin dose was calculated according to the patients age, height, and the presence of CYP2C9*2, CYP2C9*3, and VKORC1 genetic polymorphisms. The mean daily administered doses and ideal doses were compared. Analysis of variance, Student's t-test, logistic regression analysis, and Pearson's correlation analysis were used for statistical analyses.
Results: The frequency of the CYP2C9 and VKORC1 genetic polymorphisms was determined as CYP2C9*1/*1 (54.6%), *1/*2 (16.4%), *1/*3 (24.2%), *2/*3 (2.9%), *3/*3 (1.9%), wild-type VKORC1 (26.6%), heterozygote alleles (52.7%), and mutant alleles (20.8%). Patients with allelic variants were found to require lower warfarin doses, and a 64.5% correlation was found between the calculated ideal doses and the administered warfarin doses.
Conclusion: Considering CYP2C9 and VKORC1 genetic polymorphisms prior to commencing warfarin treatment will make it easier to reach target INRs and reduce the rate of complications. (Anatol J Cardiol 2016; 16: 791-6)
Birce Dilge Taşkın, Serdar Kula, Mehmet Ali Ergün, Demet Altun, Rana Olguntürk, Fatma Sedef Tunaoğlu, Ayşe Deniz Oğuz, Türkiz Gürsel. The effect of CYP2C9 and VKORC1 genetic polymorphisms on warfarin dose requirements in a pediatric population. Anatol J Cardiol. 2016; 16(10): 791-796
Corresponding Author: Demet Altun, Türkiye