Identification of CYP2C9 and VKORC1 polymorphisms in Iranian patients who are under warfarin therapy
Poopak، Behzad نويسنده Hematology Department, Islamic Azad University, Tehran Medical Branch, Tehran, Iran , , Rabieipoor، Saghar نويسنده MSc in Biotechnology, Payvand Clinical and Specialty Laboratory,Tehran, IR Iran , , SAFARI، Nazila نويسنده Radiology Department, Shiraz University of Medical Sciences, Shiraz, Iran , , Naraghi، Emadedin نويسنده MSc in Bioscience, Payvand Clinical and Specialty Laboratory, Tehran, Iran Naraghi, Emadedin , Sheikhsofla، Fatemeh نويسنده MSc in Cell and Molecular Biology, Payvand Clinical and Specialty Laboratory, Tehran, IR Iran , , Khosravipoor، Gelareh نويسنده MD, Payvand Clinical and Specialty Laboratory, Tehran, Iran 4MSc in Bioscience, Payvand Clinical and Specialty Laboratory, Tehran, Iran Khosravipoor, Gelareh
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.
Subjects and 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).
Conclusion: 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.