Genetic Determinants of Warfarin Dosing in the Han-Chinese Population

Abstract

Warfarin, a widely prescribed oral anticoagulant, is used for the prevention of thromboembolism. Polymorphisms in CYP2C9 and VKORC1 have been shown to be associated with warfarin dose requirements. However, it is likely that other genes could also affect warfarin dose. Aims: In this study, we aimed to identify additional genes influencing warfarin dosing in the Han-Chinese population. Materials & methods: In this study, we screened for SNPs in 13 genes (VKORC1, CYP2C9, CYP2C18, PROC, APOE, EPHX1, CALU, GGCX, ORM1, ORM2, factor II, factor VII and CYP4F2) and tested their associations with warfarin dosing with univariate and multiple regression analysis. Results: Polymorphisms in the VKORC1 gene have the strongest effects on warfarin dose, followed by CYP2C9*3. In addition, our results showed that CYP2C18, PROC and EPHX1 have small but significant associations with warfarin dose. In multiple regression analysis, PROC and EPHX1 explained 3% of the dose variation. The incorporation of these two genes into warfarin dosing algorithms could improve the accuracy of prediction in the Han-Chinese population.

KEYWORDS::

• CYP2C9
• Han-Chinese
• pharmacogenetics
• VKORC1
• warfarin

Financial & competing interests disclosure

This research project was supported by grants from the National Research Program for Genomic Medicine, National Science Council, Taiwan (National Clinical Core, NSC97–3112-B-001–014 and National Genotyping Center, NSC97–3112-B -001–015). Dr Yuan-Tsong Chen has applied for a patent (Application No. 11/316.406) on the use of VKORC1 polymorphisms to predict warfarin dose. 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 research project was supported by grants from the National Research Program for Genomic Medicine, National Science Council, Taiwan (National Clinical Core, NSC97–3112-B-001–014 and National Genotyping Center, NSC97–3112-B -001–015). Dr Yuan-Tsong Chen has applied for a patent (Application No. 11/316.406) on the use of VKORC1 polymorphisms to predict warfarin dose. 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.