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To establish a model for the prediction of initial standard and maintenance doses of warfarin for the Han Chinese population based on gene polymorphism: a multicenter study

  • Pharmacogenetics
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

Purpose

The purpose of this paper is to study the correlation between demographic and clinical factors and warfarin dose of patients in Chinese Han population taking warfarin and study gene polymorphisms impact of related gene loci (CYP2C9*3, VKORC1-1639G > A) on warfarin doses, to establish a model to predict initial standard dose and maintenance dose based on CYP2C9*3, VKORC1-1639G > A genotype.

Methods

The study collects the data of patients in our hospital and other subcenters which incorporates 2160 patients to establish the initial dose model and 1698 patients for the stable dose model, and sequences 26 multigene sites in 451 patients. Based on the patient’s dosage, clinical data, and demographic characteristics, the genetic and non-genetic effects on the initial dose and stable dose of warfarin are calculated by using statistical methods, and the prediction model of initial standard dose and maintenance dose can be established via multiple linear regression.

Results

The initial dose of warfarin (mg/day) was calculated as (1.346 + 0.350 × (VKORC1-1639G > A) − 0.273 × (CYP2C9*3) + 0.245 × (body surface area) − 0.003 × (age) − 0.036 × (amine-iodine) + 0.021 × (sex))2. This model incorporated seven factors and explained 55.3% of the individualization differences of the warfarin drug dose. The maintenance dose of warfarin (mg/day) was calculated as (1.336 + 0.299 × (VKORC1-1639G > A) + 0.480 × (body surface area) − 0.214 × (CYP2C9*3) − 0.074 × (amine-iodine) − 0.003 × (age) − 0.077 × (statins) − 0.002 × (height))2. This model incorporated six factors and explained 42.4% of the individualization differences in the warfarin drug dose.

Conclusion

The genetic and non-genetic factors affecting warfarin dose in Chinese Han population were studied systematically in this study. The pharmacogenomic dose prediction model constructed in this study can predict anticoagulant efficacy of warfarin and has potential application value in clinical practice.

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Funding

This work was supported by the Natural Science Foundation of Fujian Province, China (grant numbers 2018Y0037).

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Authors and Affiliations

  1. Department of Pharmacy, Fujian Medical University Union Hospital, Fuzhou, Fujian, China

    Xiaotong Xia, Jinglan Fu, Tingting Wu, Wenjun Chen, Shaojun Jiang, Meina Lv & Jinhua Zhang

  2. College of Pharmacy, Fujian Medical University, Fuzhou, Fujian, China

    Xiaotong Xia, Jinglan Fu, Tingting Wu, Wenjun Chen, Shaojun Jiang, Meina Lv & Jinhua Zhang

  3. Department of Pharmacy, Wuhan Asian Heart Hospital, Wuhan, Hubei, China

    Nianxu Huang

  4. Department of Pharmacy, The First Hospital of Lanzhou University, Lanzhou, Gansu, China

    Boxia Li

  5. Department of Pharmacy, Shandong Provincial Qianfoshan Hospital, the First Hospital Affiliated With Shandong First Medical University, Jinan, Shangdong, China

    Yan Li

  6. Department of Pharmacy, Second Affiliated Hospital, Army Medical University, Chongqing, China

    Lang Zou

  7. Department of Pharmacy, Zhengzhou Seventh People’s Hospital, Zhengzhou, Henan, China

    Dongdong Yuan

  8. Department of Pharmacy, the First People’s Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, China

    Banghua Huang

  9. Department of Pharmacy, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China

    Yufei Bei

  10. Department of Pharmacy, Huaihe Hospital of He-Nan University, Kaifeng, Henan, China

    Yuxin Liu

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  1. Xiaotong Xia
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  4. Yan Li
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Contributions

JZ and XX drafted the manuscript. JZ, HN, LB, ZL, YD, HB, BY, LY, and XX participated in the design of the study. JZ, XX, JF, TW, WC, SJ, and ML coordinated the study. All authors participated in, read, and approved the final manuscript.

Corresponding author

Correspondence to Jinhua Zhang.

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Ethics approval

This study was approved by the Ethics Committee of Union Hospital affiliated to Fujian Medical University (2016KY036, 2020KY006).

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All selected patients signed an informed consent form.

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All authors agree to publish.

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The authors declare no competing interests.

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Cite this article

Xia, X., Huang, N., Li, B. et al. To establish a model for the prediction of initial standard and maintenance doses of warfarin for the Han Chinese population based on gene polymorphism: a multicenter study. Eur J Clin Pharmacol 78, 43–51 (2022). https://doi.org/10.1007/s00228-021-03146-5

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  • DOI: https://doi.org/10.1007/s00228-021-03146-5

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