Derivation and Validation of a Genotype- Guided Warfarin Dosing Model in a Mixed Arab Population

Background Previous studies demonstrated the superiority of a genotype-guided warfarin dosing (GWD) method for warfarin initiation. International GWD models such as Gage et al model were validated in diverse populations but Arab patients were not well represented in these studies. Objective To derive and validate a GWD model in an Arab population and compare the outcomes to Gage et al model. Methods In this cross-sectional study, DNA was collected through saliva kits from a cohort of recruited Arab patients on warfarin . Clinical factors and demographics were recorded and genotyping for VKORC1 (−1639G > A) , CYP2C9*2 , CYP2C9*3 and CYP4F2*3 was performed. Subjects were randomly divided to derivation and validation cohorts. Simple and Multiple linear regression analyses were used to identify factors associated with warfarin dose and derive a warfarin dosing model. The warfarin dose was also calculated using Gage et al model. Accuracy of the 2 models were compared through the mean absolute error (MAE) and percentage of predicted warfarin doses within 20% of the actual warfarin dose Results The Arab cohort included 405 patients. In the derivation cohort (n = 270), multiple regression analysis showed a dosing model consisting of VKORC1 (−1639G > A) , CYP2C9*2 & CYP2C9*3 genotypes, along with other clinical factors (R 2 = 51.6%) (P < 0.05). When compared to Gage et al model, the Arab model had a significantly lower MAE of weekly warfarin dose (9.3 ± 7.6 mg/week vs 12.4 ± 10.4 mg/week, p = 0.03) Conclusion A model derived and validated in an Arab population had better prediction accuracy compared to an internationally validated one.