title: Identification of CYP2C9 and VKORC1 polymorphisms in Iranian patients who are under warfarin therapy.
abstract: BACKGROUND
  Although catalytic properties of different genetic polymorphisms of VKORC1 and CYP2C9 products have been identified, there is limited study available regarding warfarin dose requirement in Iranian patient population. This study investigates the impact of these polymorphisms on 115 patients, referred to Payvand Clinical and Specialty Laboratory for determining the appropriate dose of warfarin. RESULTS of the study may be applicable to individuals who are under warfarin therapy to avoid warfarin resistance or intolerance.
  
  
  METHODS
  PT-INR test was utilized as a screening method. Genotyping were performed for VKORC1 and CYP2C9 using PCR method. Statistical analyses including unpaired t-test or ANOVA and regression were done using SPSS.
  
  
  RESULTS
  VKORC1 GA was the most common genotype of VKORC1 allele among the study samples, with a rate of 57.4%. In CYP2C9 variant, 20% and 14.8% of subjects carried CYP2C9*1/*2 and CYP2C9*1/*3 genotyping, respectively. By contrast, the WT *1/*1 genotype was more abundant and dominant. The high frequency of VKORC1 (_1639) GA genotype (57.4%), was significant versus for the rest of the cohort (42.6%). In addition, a significant relationship was found between CYP2C9*1 and drug dose (P>0.021).
  
  
  CONCLUSIONS
  In this study, samples were characterized by higher frequencies of CYP2C9*1 and VKORC1 G/A, determined as higher warfarin taking doses. The results showed a significant relationship of the VCORC1 and CYP2C9 polymorphisms with warfarin sensitivity and severe side effects. Estimating right doses of warfarin to prescribe can help to reduce the risk of over- or under-anticoagulation and subsequently, the risk of thromboembolism or bleeding.
authors: DCLS, PhD in Hematology, Islamic Azad University, Tehran Medical Sciences Branch, Tehran, Iran.
authors: Behzad
authors: B
authors: Poopak
authors: MSc in Biotechnology, Payvand Clinical and Specialty Laboratory, Tehran, Iran.
authors: Saghar
authors: S
authors: Rabieipoor
authors: MSc in Molecular Oncology, Payvand Clinical and Specialty Laboratory, Tehran, Iran.
authors: Nazila
authors: N
authors: Safari
authors: MSc in Bioscience, Payvand Clinical and Specialty Laboratory, Tehran, Iran.
authors: Emadedin
authors: E
authors: Naraghi
authors: MSc in Cell and Molecular Biology, Payvand Clinical and Specialty Laboratory, Tehran, Iran.
authors: Fatemeh
authors: F
authors: Sheikhsofla
authors: MD, Payvand Clinical and Specialty Laboratory, Tehran, Iran.
authors: Gelareh
authors: G
authors: Khosravipoor
keywords: CYP2C9 and VKORC1 polymorphisms; Polymerase Change Reaction; Warfarin dose requirements