Association between Cytochrome P450 2 C9 and Vitamin K Epoxide Reductase Complex Subunit 1 Polymorphisms with Warfarin dose among Iranian Patients

Abstract

Background: Warfarin is a common anticoagulant drug that has a narrow therapeutic index; higher dose causes excessive bleeding and lower dose leads to cerebrovascular clotting and stroke in patients. Genetic factors that have been associated with warfarin response are the genes of cytochrome P450 2C9 (CYP2C9), which metabolize the more active S-enantiomer of warfarin, and vitamin K epoxide reductase (VKOR), the target site for warfarin. The present study was conducted to investigate the association between CYP2C9*2, CYP2C9*3 and VKORC1 (-1639 G>A) polymorphisms with warfarin daily dose on 118 Iranian patients under warfarin treatment. Materials and Methods: This study is comprised of 118 Iranian patients on warfarin treatment who attended the PT Clinic. Genotyping of CYP2C9*2, CYP2C9*3 and VKORC1 (-1639 G>A) was performed by PCR-RFLP method. Multiple regression model was performed for statistical analyses and P<0.05 was considered as significance level. Results: The allelic frequencies of CYP2C9*2 and CYP2C9*3 were 19% and 7%, respectively. Patients with ≥1 CYP2C9 variant allele had a significantly lower mean warfarin daily dose compared with patients with the wild-type genotype. The allelic frequencies of VKORC1 were 14.4%, 57.6% and 27.9% for GG, GA, and AA genotypes, respectively. The mean (SD) warfarin daily dose in patients with the VKORC1 (-1639) GG genotype was significantly higher than GA and AA patients. Conclusion: CYP2C9*2, CYP2C9*3 and VKORC1 (-1639 G>A) polymorphisms had significant association with warfarin daily dose. Furthermore, the daily warfarin dose was not influenced by age, height, weight and sex.

The effect of CYP2C9*2, CYP2C9*3, and VKORC1-1639 G>A polymorphism in patients under warfarin therapy in city of Kermanshah

“…In contrast to Kermanshah population, most of the subjects in Birjand showed more variant allele frequency of CYP2C9*2 , CYP2C9*3 , and VKORC1-1639 G>A as 9.1, 10, and 31.9%, respectively( 29 ). Furthermore, Dalily and Ramazani in 2012( 30 ) and Kameli, et al . in 2016( 31 ) in two separate studies in Iran reported different genotype frequencies for CYP2C9*2 , CYP2C9*3 and/or VKORC1 compared to the obtained results in our study ( Table 5 ).…”