There is a scarcity of data regarding determinants of warfarin dose requirements among Saudi patients, an ethnic group largely underrepresented in pharmacogenetic studies of warfarin. This study aimed to evaluate the prevalence of CYP2C9*2 and *3, CYP4F2 (G1347A), and VKORC1 –1639G>A genotypes and their influence on warfarin dose requirements in a cohort of Saudi individuals undergoing anticoagulation therapy. A total of 193 patients receiving long-term warfarin therapy with stable anticoagulation were enrolled. Genotyping for VKORC1 1639G>A, CYP4F2 G1347A, CYP2C92 430C>T, and CYP2C93 1075A>C was performed using TaqMan assays. Analysis of variance assessed the relationship between CYP2C9, CYP4F2, and VKORC1 genotypes and warfarin dose across two target INR groups. Backward linear regression was applied to identify both genetic and clinical factors influencing dose requirements. Individuals carrying CYP2C9 and VKORC1 variants required significantly lower warfarin doses compared to wild-type carriers, with those harboring two variant alleles needing lower doses than single-allele carriers. CYP4F2 variants did not affect warfarin dosing. Age and the presence of CYP2C9 or VKORC1 variants were inversely associated with dose requirement, whereas body surface area (BSA) showed a positive correlation. In Saudi patients, polymorphisms in CYP2C9 and VKORC1 are linked to reduced warfarin dose requirements, whereas CYP4F2 variants have no impact. Combining genetic information with clinical parameters such as age and BSA offers the most accurate prediction of warfarin dose needs in this population.
