Thromb Haemost 2012; 107(06): 1083-1091
DOI: 10.1160/TH11-12-0848
Blood Coagulation, Fibrinolysis and Cellular Haemostasis
Schattauer GmbH

A new algorithm to predict warfarin dose from polymorphisms of CYP4F2, CYP2C9 and VKORC1 and clinical variables: Derivation in Han Chinese patients with non valvular atrial fibrillation

Meng Wei
1   Department of Clinical Pharmacology, Nanjing First Hospital Affiliated to Nanjing Medical University, and Nanjing Cardiovascular Hospital, Nanjing, Jiangsu, China
3   Department of Clinical Pharmacy, China Pharmaceutical University, Nanjing, China
,
Fei Ye
2   Department of Cardiology, Nanjing First Hospital Affiliated to Nanjing Medical University, and Nanjing Cardiovascular Hospital, Nanjing, Jiangsu, China
,
Dujiang Xie
2   Department of Cardiology, Nanjing First Hospital Affiliated to Nanjing Medical University, and Nanjing Cardiovascular Hospital, Nanjing, Jiangsu, China
,
Yubing Zhu
1   Department of Clinical Pharmacology, Nanjing First Hospital Affiliated to Nanjing Medical University, and Nanjing Cardiovascular Hospital, Nanjing, Jiangsu, China
,
Junrong Zhu
1   Department of Clinical Pharmacology, Nanjing First Hospital Affiliated to Nanjing Medical University, and Nanjing Cardiovascular Hospital, Nanjing, Jiangsu, China
,
Yifu Tao
1   Department of Clinical Pharmacology, Nanjing First Hospital Affiliated to Nanjing Medical University, and Nanjing Cardiovascular Hospital, Nanjing, Jiangsu, China
,
Feng Yu
3   Department of Clinical Pharmacy, China Pharmaceutical University, Nanjing, China
› Author Affiliations
Financial support: This study was supported by a grant from Nanjing Technologies R&D Program (No. 2011YX002) and Key Technologies R&D Program of Nanjing Medical University (No. 2011NJMU202).
Further Information

Publication History

Received: 12 December 2011

Accepted after major revision: 14 March 2012

Publication Date:
29 November 2017 (online)

Summary

Few pharmacogenomic dosing regimens of warfarin have been developed for Chinese patients with non valvular atrial fibrillation (NVAF). The objective of this study was to develop a new algorithm by polymorphisms of CYP2C9, VKORC1 and CYP4F2 to predict the daily stable dose of warfarin in Chinese patients with NVAF. A total of 325 Chinese NVAF patients on stable dose of warfarin with a target international normalised ratio of 1.5 to 3.0 were recruited and divided randomly into two cohorts. CYP2C9*3, VKORC1 –1639, VKORC1 1173 and CYP4F2 were detected by ligase detection reaction method. The new algorithm was developed with multivariate linear regression in cohort 1 (260 patients) and assessed with Pearson Correlation Analysis (PCA) in cohort 2 (65 patients). From 260 enrolled patients, the model (R2 = 51.7%) was developed as: Dose = 3.47 − 0.022 (AGE) + 0.017 (WT) + 0.189 (PTE) − 0.283 (β-blocker) − 0.471 (AMIO) − 0.586 (CYP2C9 *1/*3) − 0.296 (VKORC1 CT) – 0.648 (VKORC1 TT) + 0.219 (CYP4F2 TT). PCA displayed that the algorithm was good (r = 0.658). The residual plots revealed that the predicted doses by the algorithm tend to be overestimated when lower doses were administered to patients and to be underestimated in higher doses. The algorithm developed by us might predict warfarin dose used by Chinese NVAF patients.

 
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