title: Warfarin dose requirement in Turkish patients: the influences of patient characteristics and polymorphisms in CYP2C9, VKORC1 and factor VII.
abstract: BACKGROUND
  To determine the contribution of cytochrome P4502C9 (CYP2C9), vitamin K epoxide reductase (VKORC1) and factor VII genotypes, age, body mass index (BMI), international normalized ratio (INR) and other individual patient characteristics on warfarin dose requirements in an adult Turkish population.
  
  
  METHODS
  Blood samples were collected from 101 Turkish patients. Genetic analyses for CYP2C9*2 and *3, VKORC1 -1639 G>A and factor VII -401 G>T polymorphisms were performed. Age, INR, BMI values and other individual patient characteristics were also recorded.
  
  
  RESULTS
  The mean daily warfarin dosage was significantly higher in patients with the CYP2C9*1/*1 genotype than in the CYP2C9*2/*2 and CYP2C9*1/*3 groups (p ≤ 0.05). With respect to the VKORC1 -1639 G>A polymorphism, the mean warfarin daily dose requirement was higher in the wild type group compared to the heterozygous group (p≤0.001). The mean daily dose requirement for patients with the GG form of factor VII was significantly higher than that of patients with the TT genotype (p ≤ 0.05). Age, gender, BMI, INR had no statistically significant correlation with warfarin dose (p ≥ 0.05).
  
  
  CONCLUSIONS
  Polymorphisms in CYP2C9, VKORC1 and factor VII did partially affect daily warfarin dose requirements, while age, gender, BMI and INR do not. However, further case-control studies with a larger study size and different genetic loci are needed to confirm our study.
authors.affiliation: Pharmacology Department,Medical Faculty, Eskisehir Osmangazi University, Eskisehir, Turkey.
authors.forename: E
authors.initials: E
authors.lastname: Yildirim
authors.affiliation: Pharmacology Department,Medical Faculty, Eskisehir Osmangazi University, Eskisehir, Turkey.
authors.forename: K
authors.initials: K
authors.lastname: Erol
authors.affiliation: Cardiology Department Medical Faculty, Eskisehir Osmangazi University, Eskisehir, Turkey.
authors.forename: A
authors.initials: A
authors.lastname: Birdane
keywords: CYP2C9; VKORC1; Warfarin; factor VII; polymorphism