Ann Lab Med 2020; 40(3): 216-223  https://doi.org/10.3343/alm.2020.40.3.216
Development and Validation of a Novel Warfarin Dosing Algorithm for Korean Patients With VKORC1 1173C
Eun Hye Cho, M.D.1,*, Kyunghoon Lee, M.D.2,*, Mina Yang, M.D.3, Rihwa Choi, M.D.1,4, Sun-Young Baek, M.S.5, Insuk Sohn, Ph.D.5, June Soo Kim, M.D.6, Young Keun On, M.D.6, Oh Young Bang, M.D.7, Hyun-Jung Cho, M.D.8, and Soo-Youn Lee, M.D.1,9,10
1Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea; 2Department of Laboratory Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea; 3Department of Laboratory Medicine, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, Korea; 4Department of Laboratory Medicine, Green Cross Laboratories, Yongin, Korea; 5Statistics and Data Center, Samsung Medical Center, Seoul, Korea; 6Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine; 7Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea; 8Department of Laboratory Medicine, Konyang University Hospital, Konyang University School of Medicine, Daejeon, Korea; 9Department of Clinical Pharmacology & Therapeutics, Samsung Medical Center, Seoul, Korea; 10Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Korea
Corresponding author: Soo-Youn Lee, M.D., Ph.D.
Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea
Tel: +82-2-3410-1834 Fax: +82-2-3410-2719 E-mail: suddenbz@skku.edu

Hyun-Jung Cho, M.D., Ph.D.
Department of Laboratory Medicine, Konyang University Hospital, Konyang University School of Medicine, 158 Gwangeodong-ro, Seo-gu, Daejeon 35365, Korea
Tel: +82-42-600-9273 Fax: +82-42-600-9272 E-mail: hjchomd@kyuh.ac.kr

* These authors contributed equally to this work.
Published online: May 1, 2020.
© Korean Society for Laboratory Medicine. All rights reserved.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Background: Differences in the performance of suggested warfarin dosing algorithms among different ethnicities and genotypes have been reported; this necessitates the development of an algorithm with enhanced performance for specific population groups. Previous warfarin dosing algorithms underestimated warfarin doses in VKORC1 1173C carriers. We aimed to develop and validate a new warfarin dosing algorithm for Korean patients with VKORC1 1173C.
Methods: A total of 109 patients carrying VKORC1 1173CT (N=105) or 1173CC (N=4) were included in this study. Multiple regression analysis was performed to deduce a new dosing algorithm. Following literature searches for genotype-guided warfarin dosing algorithms, 21 algorithms were selected and evaluated using the correlation coefficient (ρ) of actual dose and estimated dose, mean error, and root mean square error.
Results: The developed algorithm is as follows: maintenance dose (mg/week)=exp [3.223−0.009×(age)+0.577×(body surface area [BSA])+0.178×(sex)−0.481×(CYP2C9 genotype)+0.227×(VKORC1 genotype)]. Integrated variables explained 44% of the variance in the maintenance dose. The predicted and actual doses showed moderate correlation (ρ=0.641) with the best performance with a mean error of -1.30 mg/week. The proportion of underestimated groups was 17%, which was lower than with the other algorithms.
Conclusions: This is the first study to develop and validate a warfarin dosing algorithm based on data from VKORC1 1173C carriers; it showed superior predictive performance compared with previously published algorithms.
Keywords: Warfarin, Genotype, VKORC1, Korea, Performance, Dosing algorithm



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