Association of VKORC1 and CYP2C9 gene polymorphisms with warfarin dose requirements in a representative Iranian population with cardiac valve replacement surgery.

Background: Warfarin is a commonly used oral anticoagulant for managing thromboembolic events after cardiac valve surgery. However, its optimal dose varies between individuals, often requiring trial and error to determine. This study aimed to investigate the association of polymorphisms in the CYP2C9 and VKORC1 genes with warfarin dose requirements in an Iranian population undergoing cardiac valve replacement.

Materials and methods: A total of 140 patients recieving warfarin after cardiac valve replacement surgery were enrolled. Patients were monitored for their daily warfarin dose and international normalized ratio for at least 3 months post-surgery. Genotyping of CYP2C9 rs1057910 and VKORC1 rs2884737 was conducted using the tetra-primer amplification refractory mutation system -PCR method. Associations between genotypes and warfarin dose were analyzed using linear regression. A P value < 0.05 was considered statistically significant.

Results: Patients with the heterozygous AC genotype of CYP2C9 rs1057910 required a significantly lower warfarin dose than those with the wild-type genotype (P < 0.05). Although variation in warfarin dose was observed among patients with different VKORC1 rs2884737 genotypes, the association was not statistically significant. Including patients' demographic covariates in the regression model did not alter the observed genotype-dose associations.

Conclusion: The CYP2C9 rs1057910 variant was significantly associated with daily warfarin dose requirements, suggesting its potential role in guiding idividualized dosing. In contrast, VKORC1 rs2884737 showed no significant association in this population, despite previous findings in other ethnic groups.