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Genetic Factors Influencing Warfarin Dose in Han Chinese Population: A Systematic Review and Meta-Analysis of Cohort Studies

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Abstract

Objective

To investigate the association of single nucleotide polymorphisms (SNPs) of various genes known to influence mean daily warfarin dose (MDWD) in the Han Chinese population.

Methods

The study is a systematic review and meta-analysis. Selected studies retrieved by searching Pubmed, Embase (Ovid), Medline, CNKI, Wanfang data, and SinoMed (from their inception to 31 August 2022) for the cohort studies assessing genetic variations that may possibly influence MDWD in Chinese patients were included.

Result

A total of 46 studies including a total of 10,102 Han Chinese adult patients were finally included in the meta-analysis. The impact of 20 single nucleotide polymorphisms (SNPs) in 8 genes on MDWD was analyzed. The significant impact of some of these SNPs on MDWD requirements was demonstrated. Patients with CYP4F2 rs2108622 TT, EPHX1 rs2260863 GC, or NQO1 rs1800566 TT genotype required more than 10% higher MDWD. Furthermore, patients with ABCB1 rs2032582 GT or GG, or CALU rs2290228 TT genotype required more than 10% lower MDWD. Subgroup analysis showed that patients with EPHX1 rs2260863 GC genotype required 7% lower MDWD after heart valve replacement (HVR).

Conclusion

This is the first systematic review and meta-analysis assessing the association between single nucleotide polymorphisms (SNPs) of various genes known to influence MDWD besides CYP2C9 and VKORC1 in the Han Chinese population. CYP4F2 (rs2108622), GGCX (rs12714145), EPHX1 (rs2292566 and rs2260863), ABCB1 (rs2032582), NQO1 (rs1800566), and CALU (rs2290228) SNPs might be moderate factors affecting MDWD requirements.

Registered information

PROSPERO International Prospective Register of Systematic Reviews (CRD42022355130).

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Authors and Affiliations

  1. Department of Pharmacy, Beijing Hospital; National Center of Gerontology; Institute of Geriatric Medicine, Chinese Academy of Medical Sciences; Beijing Key Laboratory of Assessment of Clinical Drugs Risk and Individual Application (Beijing Hospital), No. 1 Dahua Road, Dongdan, Dongcheng District, Beijing, 100730, China

    Zinan Zhao, Fei Zhao, Yatong Zhang, Xin Hu, Ming Zhao & Pengfei Jin

  2. Department of Cardiology, Beijing Hospital, National Center of Gerontology; Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, 100730, China

    Xiang Wang, Deping Liu & Junpeng Liu

  3. Department of Pharmacy, Beijing Children’s Hospital, Capital Medicine University, National Center for Children’s Health, Beijing, 100045, China

    Chao Tian

  4. Department of Pharmacy, Peking University Third Hospital, Beijing, 100191, China

    Shujie Dong

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  1. Zinan Zhao
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Funding

This work was financially supported by China National Key R&D Program (no. 2020YFC2008305).

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Zinan Zhao, Fei Zhao, Xiang Wang, Deping Liu, Junpeng Liu, Yatong Zhang, Xin Hu, Ming Zhao, Tian Chao, Shujie Dong, and Pengfei Jin declared no potential conflicts of interests/competing interests that might be relevant to the contents of this manuscript.

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Pengfei Jin and Zinan Zhao conceptualized the research. Xiang Wang, Shujie Dong, and Chao Tian conducted statistical analysis. Deping Liu, Yatong Zhang, and Xin Hu contributed to data interpretation. Junpeng Liu, Fei Zhao, and Ming Zhao contributed to study searching. Zinan Zhao wrote the manuscript draft. All authors contributed to the draft revision and approved the final draft of the manuscript.

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Zhao, Z., Zhao, F., Wang, X. et al. Genetic Factors Influencing Warfarin Dose in Han Chinese Population: A Systematic Review and Meta-Analysis of Cohort Studies. Clin Pharmacokinet 62, 819–833 (2023). https://doi.org/10.1007/s40262-023-01258-y

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