The Genetic Polymorphisms of CYP2C9 and VKORC1 in the Saudi Population and Their Impact on Anticoagulant Management

Background and objectives: Warfarin is a commonly used anticoagulant with a narrow therapeutic index that requires a precise dose to achieve efficacy and safety. Genetic variations in the CYP2C9 and VKORC1 genes significantly contribute to individual responses to warfarin, influencing both drug metabolism and pharmacodynamics. The current study aims to investigate the frequency of CYP2C9 and VKORC1 variant genotypes and determine the appropriate warfarin dosage for patients in Saudi Arabia. Materials and Methods: Blood samples were collected from 100 Saudi patients undergoing treatment with warfarin. DNA was extracted and purified from the whole blood, and variants in the CYP2C9 and VKORC1 genes were analyzed using multiplex PCR techniques. Results: The analysis revealed that the VKORC1 GG genotype was the most common, at 54%, followed by GA at 30%, and the AA at 16%. For CYP2C9, the *1/*1 genotype predominated at 71%, whereas the *1/*2 genotype was found in 14%, the *1/*3 genotype was found in 11%, and the *2/*3 genotype was found in in 2%, being less frequently observed. Patients with VKORC1 GG required significantly higher warfarin doses than those with GA and AA genotypes. Similarly, CYP2C9 *1/*1 patients required higher doses than those with *1/*3 and *2/*3 variants. No significant differences in INR levels across genotypes were found, indicating that while genetic variations influence dosing, they do not significantly alter the therapeutic INR range. Conclusions: The findings indicate that genetic variations influence drug metabolism and response in the Saudi population, aligned with global studies. Such tailored approaches could enhance treatment efficacy and reduce adverse effects, underscoring the role of pharmacogenomics in patient care and optimizing warfarin therapy in unique genetic populations.