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

Abstract

Polymorphism in the genes encoding <i>CYP2C9</i> enzyme and <i>VKORC1</i> reductase significantly influence warfarin dose requirement since patients with <i>CYP2C9*2</i>, <i>CYP2C9*3</i> and <i>VKORC1</i> 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 <i>VKORC1-1639 G>A</i>, <i>CYP2C9*2</i>, and <i>CYP2C9*3</i>. Polymorphism genotyping was performed by sequencing as well as polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) using restriction enzymes of <i>MspI, AVAII</i> and <i>KpnI</i>, respectively. The frequencies of <i>VKORC1</i>-1639 GG, GA, and AA genotypes were 42%, 36%, and 22%, respectively and for <i>CYP2C9</i> 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 <i>VKORC1</i>-1639A allele was 42.3% and the frequencies of <i>CYP2C9*2</i> and *3 alleles were 14% and 5.4%, respectively. It was indicated that low warfarin dose requirements are strongly associated with the presence of <i>CYP2C9</i> and <i>VKORC1-1639</i> variant alleles. Our results confirmed the supply to understand the distribution of genomic biomarkers related to the drugs metabolism for future planning health programs.