Chen Hao, Tong Jia-bin, LU You, Chong Jia, Tian Wei-meng, LI Peng, DU Xin, MA Chang-sheng and Yang Jie-fu
Abstract Objective: The objective of this study was to develop a new warfarin dosing algorithm based on polymorphisms in CYP2C9 and VKORC1 gene with other demographic variables from a retrospective study for accurate prediction of maintenance dosage in Han subjects with AF in China. Methods: A total of 131 Chinese AF patients with steady warfarin daily dosage (INR reach target range) were recruited from Beijing Hospital during January to November 2011. Blood samples were taken to detect genotype distribution and allelic frequencies of target SNPs: rs1057910 and rs9934438 by direct gene sequencing technique. Demographics variables were recorded during regular visit. All variables for multivariate regression analysis were those significant predictors derived from the univariate analysis, thereafter a stepwise multiple regression analysis was performed to deduce a new dosing algorithm. Results: Four significant predictors (CYP2C9 A1075C, VKORC1 C1173T, age and BSA) derived from univariate analysis were carried to step-wise multiple regression analysis and a new algorithm was deduced (R2=0.436). Their weights for predicting of warfarin dosage were 20.8%, 11.5%, 4.5% and 6.8%, respectively. Conclusion: For Chinese Han patients with AF who accepted oral anticoagulation drug therapy, age, BAS, CYP2C9 A1075C and VKORC1 C1173T are the predictors which highly correlated to variation of warfarin dosage. In dosing prediction system, the weight of pharmacogenetic factors is more robust than that of clinical variables. The interpretation of our algorithm could account for nearly half of heterogeneity of individualized warfarin dosage.
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