VKORC1 and CYP2C9 Genetic Variants Coumarin Response in the Mestizo-Mexican Population

Introduction: Polymorphisms in the genetic variations of vitamin K epoxide reductase complex subunit 1 (VKORC1) and Cytochrome P450 subfamily IIC polypeptide 9 (CYP2C9) have been shown to cause variability in anticoagulant response across various ethnic groups. In the Mestizo-Mexican population, with their Amerindian-European and African-Asiatic ancestral origins, the response is expected to differ as well. This study aims to evaluate the anticoagulant response to coumarin in Mestizo-Mexican patients with mechanical heart valve prostheses.Method: DNA was extracted from blood samples using a commercial genomic DNA purification kit. The polymorphisms rs1799853 CT in the CYP2C9*2 gene and rs9923231VKORC1-G1639A gene were determined using real-time PCR. All patients initially received a dose of 8 mg/day of coumarin, which was adjusted on the second day based on international normalized ratio (INR) levels until reaching a result of 2.5-3.5.Results : Seventy-six patients with an average age of 58±11 years were undergoing mitral (n=44) and aortic (n=32) valve replacement. Patients carrying GG haplotypes in the rs9923231VKORC1-G1639A gene variant required a significantly higher coumarin dose to reach the therapeutic range compared to those with GA and AA haplotypes (p=0.001). The rs1799853 polymorphism of the CYP2C9*2 A/C gene showed no significant differences between AA, AC, and CC haplotypes (p>0.05).Conclusion : In the Mestizo-Mexican population, individuals carrying the rs9923231 VKORC1 gene with GG haplotypes exhibited a hyporeactive anticoagulant response compared to those with GA and AA haplotypes, which showed normal and hyperreactive responses, respectively. There were no significant differences in the response of the CYP2C9*2 haplotypes AC carriers.