Effects of Rare CYP2C9 Alleles on Stable Warfarin Doses in Chinese Han Patients with Atrial Fibrillation

Abstract

Aim: Gene polymorphisms are critical in warfarin dosing variation. Here, the role of rare CYP2C9 alleles on warfarin doses in Chinese Han patients was investigated. Methods: A retrospective study recruited 681 warfarin treated atrial fibrillation patients. The genetic and clinical data were collected. Dose-related variables were selected by univariate analyses and the warfarin-dosing algorithm was derived by multivariate regression analysis. Results: Three rare CYP2C9 alleles (CYP2C9*13, *16 and *60) were associated with lower stable doses. Inclusion of the rare CYP2C9 alleles in the prediction model added an extra 3.7% warfarin dose predictive power. Conclusion:CYP2C9*13, *16 and *60 was associated with lower stable warfarin doses in Chinese patients. The algorithm including rare CYP2C9 alleles tends to more accurately predict stable warfarin doses.

Keywords::

• atrial fibrillation
• CYP2C9
• gene polymorphism
• warfarin-dosing algorithm
• warfarin

Financial & competing interests disclosure

This study was funded by the National Science Foundation of China (no. 81570307) and the CAMS Innovation Fund for Medical Sciences (no. 2018-I2M-1-002). 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.

Elsevier Premium Language Editing Services was utilized in 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.

Data sharing statement

Deidentified individual participant data underlying the results reported in this article can be made available to researchers who provide a methodologically sound proposal, beginning 3 months and ending 5 years following article publication. Proposals shouldbe directed to the corresponding author. To gain access, data requestors will need to sign a data access agreement.

Additional information

Funding

This study was funded by the National Science Foundation of China (no. 81570307) and the CAMS Innovation Fund for Medical Sciences (no. 2018-I2M-1-002). 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. Elsevier Premium Language Editing Services was utilized in this manuscript.