Abstract
Background and Objective: The variation in response to Warfarin is related to clinical and genetic determinants. This study aimed to explore the effect of CYP2C9*2 and VKORC-7639G/A polymorphism on Warfarin dose requirements in Sudanese patients. Materials and Methods: This was a descriptive cross-sectional study conducted in the Sudan heart centre, Khartoum-Sudan. A total of 165 Sudanese patients under Warfarin therapy attending the Sudan heart centre during the study period were selected. Citrated anticoagulated whole blood samples were collected from all participants. Plasma was separated for PT-INR measurements, while Buffy coat was used for genomic DNA extraction and subsequent PCR-RFLP analysis for CYP2C9430C>T and VKORC1-7639G>A polymorphism. Results:The study showed patients that carriers of CYP2C9430C> Tor VKORC1-7639G>A polymorphisms had significantly lower Warfarin dose requirements compared with wild types. The p = 0.04 and 0.004, respectively. The study also revealed that the combined effects of clinical and genetic factors explained 30.1% of the variation in Warfarin dose. The clinical factors include age, gender, indication for therapy, comorbid disease and concurrent medications. In this study, the VKORC1-7639G>A polymorphism was the major predictor of Warfarin dose, explaining 10.8% of the variation in dose requirements. A regression model including VKORC1 genotype and an indication of Warfarin therapy was a significant predictor of stable dose (p = 0.001). Conclusion: In Sudanese patients, Warfarin dose is influenced by VKORC1-7639G>A and CYP2C9 430C>T polymorphisms and therapeutic indication. Therefore, including pharmacogenetics data in the dosing algorithm may improve Warfarin therapy accuracy in Sudanese subjects.