title: The effect of CYP2C9 and VKORC1 genetic polymorphisms on warfarin dose requirements in a pediatric population.
abstract: 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.
  
  
  
  Fifty-eight pediatric patients with cardiac disease, thrombophilia, or other conditions, taking a stable warfarin dose, aged 0.2-18 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 patient's 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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Department of Pediatric Neurology, Ankara Children's Hematology Oncology Training and Research Hospital, Ankara-Turkey.
authors.forename: Birce
authors.initials: B
authors.lastname: Dilge Taşkın
authors.affiliation: Department of Pediatric Cardiology, Faculty of Medicine, Gazi University, Ankara-Turkey.
authors.forename: Serdar
authors.initials: S
authors.lastname: Kula
authors.affiliation: Department of Medical Genetics, Faculty of Medicine, Gazi University, Ankara-Turkey.
authors.forename: Mehmet Ali
authors.initials: MA
authors.lastname: Ergün
authors.affiliation: Department of Pediatrics, Etimesgut Air Force Hospital, Ankara-Turkey. draltundemet@gmail.com.
authors.forename: Demet
authors.initials: D
authors.lastname: Altun
authors.affiliation: Department of Pediatric Cardiology, Faculty of Medicine, Gazi University, Ankara-Turkey.
authors.forename: Rana
authors.initials: R
authors.lastname: Olguntürk
authors.affiliation: Department of Pediatric Cardiology, Faculty of Medicine, Gazi University, Ankara-Turkey.
authors.forename: Fatma Sedef
authors.initials: FS
authors.lastname: Tunaoğlu
authors.affiliation: Department of Pediatric Cardiology, Faculty of Medicine, Gazi University, Ankara-Turkey.
authors.forename: Ayşe Deniz
authors.initials: AD
authors.lastname: Oğuz
authors.affiliation: Department of Pediatric Hematology, Faculty of Medicine, Gazi University, Ankara-Turkey.
authors.forename: Türkiz
authors.initials: T
authors.lastname: Gürsel
mesh_terms: D000293:Adolescent; D000925:Anticoagulants / Q000008:administration & dosage* / Q000009:adverse effects; D001189:Aryl Hydrocarbon Hydroxylases; D002648:Child; D002675:Child, Preschool; D065729:Cytochrome P-450 CYP2C9 / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D007223:Infant; D008297:Male; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D064417:Vitamin K Epoxide Reductases / Q000235:genetics*; D014859:Warfarin / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D000925:Anticoagulants; D014859:Warfarin; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; C578523:VKORC1 protein, human; D064417:Vitamin K Epoxide Reductases