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

Zohreh Hosseinkhani, Mona Sadeghalvad, Fathemeh Norooznezhad, Reza Khodarahmi, Mohammad Fazilati, Azadeh Mahnam, Ali Fattahi, Kamran Mansouri

Abstract


Polymorphism in the genes encoding CYP2C9 enzyme and VKORC1 reductase significantly influence warfarin dose requirement since patients with CYP2C9*2, CYP2C9*3 and VKORC1 mutant alleles require lower warfarin maintenance doses. Studies have reported the ethnic variations in the frequency of these genes within the various populations in Iran and other parts of the world. However, no such study has been done yet on Kurdish population in Kermanshah. From Kurdish population of Kermanshah province in Iran, a total of 110 patients who had heart surgery and taking warfarin, were genotyped for polymorphisms of VKORC1-1639 G>A, CYP2C9*2, and CYP2C9*3. Polymorphism genotyping was performed by sequencing as well as polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) using restriction enzymes of MspI, AVAII and KpnI, respectively. The frequencies of VKORC1-1639 GG, GA, and AA genotypes were 42%, 36%, and 22%, respectively and for CYP2C9 1*/1*, 1*/2*, 2*/2*, 1*/3*, 3*/3*, 2*/3* were 71%, 17%, 5.4%, 1.8%, 4.5%, and 0%, respectively. The frequency of VKORC1-1639A allele was 42.3% and the frequencies of CYP2C9*2 and *3 alleles were 14% and 5.4%, respectively. It was indicated that low warfarin dose requirements are strongly associated with the presence of CYP2C9 and VKORC1-1639 variant alleles. Our results confirmed the supply to understand the distribution of genomic biomarkers related to the drugs metabolism for future planning health programs.

Keywords


Cytochrome P-450 CYP2C9; International normalized ratio; Polymorphism; Vitamin K1 epoxide reductase; Warfarin.

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