Abstract
Objectives
Despite its wide usage, warfarin therapy remains challenging due to its narrow therapeutic index, inter-individual response variability, and risk of bleeding. Previous reports have suggested that polymorphisms in VKORC1 and CYP2C9 genes could influence warfarin therapy. Herein, we investigated whether VKORC1 −1173C>T, CYP2C9*2, and CYP2C9*3 gene polymorphisms are associated with warfarin dose adjustment and related bleeding events.
Methods
This cross-sectional study was conducted on Saudi adults receiving warfarin for more than 1 month. Their demographics and relevant clinical data were obtained. Genotyping for VKORC1 −1173C>T, CYP2C9*2, and CYP2C9*2 genotypes was performed.
Results
Patients who are homozygous for the mutant T allele VKORC1 T/T required the lowest warfarin daily maintenance dose, compared to VKORC1 C/T and VKORC1 C/C. Similarly, there was a significant reduction in warfarin daily maintenance dose among CYP2C9*1/*3 and CYP2C9*1/*2 groups compared to CYP2C9*1/*1. However, we found no significant correlation between the studied polymorphisms and warfarin-associated bleeding.
Conclusions
Similar to other populations, the VKORC1 and CYP2C9 gene polymorphisms are significantly associated with warfarin dosage in Saudi patients. The presence of at least one copy of the mutant alleles for VKORC1 −1173C>T, CYP2C9*2, and CYP2C9*3 is associated with a significant reduction in warfarin maintenance dose.
Funding source: Alfaisal University
Award Identifier / Grant number: 16307
Acknowledgments
The authors would like to thank Mrs. Shisamma Emmanual for facilitating Sample collection. The completion of this study would not have been accomplished without the support of Professor Khaled Al- Kattan. We are grateful for Dr. Emad Masuadi for completing the statistical analyses.
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Research funding: This study was supported by Alfaisal University Office of Research Innovation and Commercialization grant (Grant # 16307).
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Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
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Competing interests: Authors state no conflict of interest.
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Informed consent: Informed consent was obtained from all individuals included in this study.
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Ethical approval: Research involving human subjects complied with all relevant national regulations, institutional policies and is in accordance with the tenets of the Helsinki Declaration (as revised in 2013) and has been approved by the authors’ Institutional Review Board (IRB ORA/392/38).
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