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Influence of genetic polymorphisms in cytochrome P450 oxidoreductase on the variability in stable warfarin maintenance dose in Han Chinese

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

Abstract

Purpose

The aim of this study was to investigate whether any of the single-nucleotide polymorphisms (SNPs) in the POR gene were significantly associated with CYP activity and expression, and could contribute to the total variability in stable warfarin maintenance doses in Han Chinese.

Methods

A total of 408 patients treated at the First Affiliated Hospital of Sun Yat-Sen University were eligible for the study and had attained a stable warfarin maintenance dose at the start of the investigation. Demographics, warfarin maintenance doses, and concomitant medications were documented. Genomic DNA was extracted from peripheral blood samples and genotyped for ten SNPs (CYP 2C9*2 and *3, CYP4F2 rs2108622, VKORC1 −1639C>T, and potential POR genes of rs10239977, rs3815455, rs41301394, rs56256515, rs1057868, and rs2286823) using the Sequenom MassARRAY genotyping system.

Results

A predictive model of warfarin maintenance dose was established and indicated that age, gender, body surface area, aspirin use, CYP2C9*3, CYP4F2 rs2108622, VKORC1 −1639C>T, and POR*37 831–35C>T accounted for 42.4 % of dose variance in patients undergoing anticoagulant treatment. The contribution of POR*37 831–35C>T to warfarin dose variation was only 3.9 %.

Conclusions

For the first time, the SNP POR*37 831–35C>T was confirmed as a minor but statistically significant factor associated with interindividual variation in warfarin maintenance dose in Han Chinese. The POR*37 gene polymorphism should be considered in future algorithms for faster and more reliable achievement of stable warfarin maintenance doses.

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Acknowledgments

Contributions of authors

1. Wu-Tao Zeng – bidding document applicant and foundation holder.

2. Qing Xu, Wei-Yan Chen, Hui Shi – literature review and innovation.

3. Xiu-Ting Sun, Yi-Ying Yang – management of demographics and blood samples.

4. Cheng-Hsun Li – isolation of genomic DNA, Sequenom MassArray statistical analysis.

5. Xiang Wang, Zhi-Sheng Yang – data analysis.

6. All contributors – discussion composition.

Author information

Authors and Affiliations

  1. The First Affiliated Hospital of Sun Yat-sen University, No.58 Zhongshan Rd.2, Guangzhou, Guangdong, 510080, People’s Republic of China

    Wu-Tao Zeng, Qing Xu, Cheng-Hsun Li, Xiu-Ting Sun, Xiang Wang, Yi-Ying Yang, Hui Shi & Zhi-Sheng Yang

  2. The Second Affiliated Hospital of Guangzhou Medical University, No. 250 Changgangdong Rd, Guangzhou, Guangdong, 510260, People’s Republic of China

    Wei-Yan Chen

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  1. Wu-Tao Zeng
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  2. Qing Xu
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Corresponding author

Correspondence to Cheng-Hsun Li.

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Funding

This study was funded by the National Natural Science Foundation of China (grant nos. 81170215, 81270299).

Lab institution Key Laboratory on Assisted Circulation, Ministry of Health, China ( lab nos 236194010)

Conflict of interest

All authors have declared no support from any organization for the submitted work; no financial relationships with any organizations that might have an interest in the submitted work in the previous 3 years; no other relationships or activities that could appear to have influenced the submitted work.

Ethical approval

All procedures performed in study involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. This study was approved by the ethics committee of the First Affiliated Hospital of Sun Yat-Sen University (reference no.: 2013166).

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Zeng, WT., Xu, Q., Li, CH. et al. Influence of genetic polymorphisms in cytochrome P450 oxidoreductase on the variability in stable warfarin maintenance dose in Han Chinese. Eur J Clin Pharmacol 72, 1327–1334 (2016). https://doi.org/10.1007/s00228-016-2098-x

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  • DOI: https://doi.org/10.1007/s00228-016-2098-x

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