Impact of Cyp2c9 and Vkorc1 Genetic Variants on Warfarin Therapy Optimization in South Indian Population With Venous Thromboembolism

Background: Genetic polymorphisms in CYP2C9 and VKORC1 significantly influence warfarin dosing requirements, yet population-specific data from South India remains limited. Aim &Objectives: To determine the distribution of VKORC1 (-1639G>A) and CYP2C9 (*2 and *3) polymorphisms in South Indian VTE patients and their impact on anticoagulation response and warfarin dosage. Methods: This cross-sectional study examined 192 participants (96 warfarin-treated venous thromboembolism patients and 96 controls) from North Coastal Andhra Pradesh. DNA was extracted and genotyped using PCR-RFLP for CYP2C9*2, CYP2C9*3, and VKORC1 (-1639G>A) polymorphisms. Correlations between genotypes, warfarin dosing, and INR values were analysed. Results: VKORC1 genotype frequencies were GG: 64.6%, GA: 22.9%, AA: 12.5%. CYP2C9 wild-type frequency was 29.2%. Patients with VKORC1 AA genotype required significantly lower warfarin doses (1.14 ± 1.08 mg/day) compared to GG genotype (3.59 ± 1.44 mg/day) while achieving higher INR values (2.88 ± 0.41 vs 2.62 ± 0.38). This represented a 68% dose reduction in variant carriers. Conclusion: CYP2C9 and VKORC1 polymorphisms substantially influence warfarin sensitivity in South Indian populations, with variant carriers requiring markedly reduced doses. These findings support implementing pharmacogenetic-guided dosing strategies for optimizing anticoagulant therapy in this population.