Impact of CYP2C9, VKORC1, ApoE and ABCB1 Polymorphisms on Stable Warfarin Dose Requirements in Elderly Chinese Patients

Abstract

Aim: To analyze the impact of nongenetic factors and gene polymorphisms on warfarin dose requirements in elderly Shanghai Han Chinese patients. Materials & methods: Genotypes of CYP2C9 (rs1799853 and rs1057910), FPGS (rs7856096), ApoE (rs7412 and rs429358), GGCX (rs699664 and rs12714145), EPHX1 (rs4653436, rs1877724, rs1051740 and rs1131873), NQO1 (rs1800566 and rs10517), ABCB1 (rs1045642), VKORC1 (rs9923231) and CYP4F2 (rs2108622) in 214 patients with stable warfarin dose were determined and their demographic characteristics were recorded. Results: Multiple linear regression analysis revealed that VKORC1 rs9923231, CYP2C9*3 rs1057910, ApoE rs7412, age, BMI and concomitant amiodarone could explain 37.0% of the individual variations of daily stable warfarin dose. Conclusion:VKORC1 rs9923231, CYP2C9*3 rs1057910, ApoE rs7412, age, BMI and concomitant amiodarone play an important role in stable dose variation of warfarin in elderly Shanghai Han Chinese patients, whereas ABCB1 rs1045642 is not a significant genetic factor.

Keywords::

• ABCB1
• ApoE
• CYP2C9
• VKORC1
• gene polymorphism
• stable warfarin dose

Author contributions

W Li was responsible for study design. P Zhao was responsible for statistical analysis. L Chen and G Shi collected and analyzed the data. X Lai and L Li were responsible for patients enrolled. All authors read and approved the final manuscript. J Dong was in charge of the whole study and wrote the paper.

Acknowledgments

The authors would like to thank the enrolled patients and staff who participated in this study. The authors gratefully acknowledge the doctors and nurses of the Department of cardiology, respiratory medicine and neurology of Gongli Hospital of Pudong New Area, The Second Military Medical University (Shanghai, PR China).

Financial & competing interests disclosure

This study was supported by Minsheng Scientific Research (medical and health) Funded of Science and Technology Development of Shanghai Pudong New Area (2016 PKJ2016-Y58), Excellent Young Medical Personnel Funded of the Health and Family Planning Commission Construction of Shanghai Pudong New Area (2017 PWRq2017-14), Natural Science Foundation of China (81803632), Key Disciplines of Clinical Pharmacy of Health and Family Planning Commission of Shanghai Pudong New Area (2017 PWKxk2017-13), the Key Specialty of Clinical Pharmacy of Municipal Health and Family Planning Commission of Shanghai, the Key Specialty Construction Project of Shanghai Municipal Commission of Health and Family Planning (ZK2019A08). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Additional information

Funding

This study was supported by Minsheng Scientific Research (medical and health) Funded of Science and Technology Development of Shanghai Pudong New Area (2016 PKJ2016-Y58), Excellent Young Medical Personnel Funded of the Health and Family Planning Commission Construction of Shanghai Pudong New Area (2017 PWRq2017-14), Natural Science Foundation of China (81803632), Key Disciplines of Clinical Pharmacy of Health and Family Planning Commission of Shanghai Pudong New Area (2017 PWKxk2017-13), the Key Specialty of Clinical Pharmacy of Municipal Health and Family Planning Commission of Shanghai, the Key Specialty Construction Project of Shanghai Municipal Commission of Health and Family Planning (ZK2019A08). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.