Association of Genetic Polymorphisms with Warfarin Dose Requirements in Chinese Patients

摘要

Objective: Warfarin is a commonly used anticoagulant with a narrow therapeutic range and large interindividual differences in dosing requirements. Previously, studies have identified that the interindividual variability was influenced by varieties of factors, including age, body size, vitamin K intake, interacting medications, as well as genetic variants. We aimed to investigate the effect of single-nucleotide polymorphisms (SNPs) on the interindividual variability of warfarin dose requirements in Chinese patients. Methods: The study population consisted of 300 patients with a stable maintenance dose of warfarin. We examined SNPs in eight genes involving in the biotransformation and mode of action of warfarin (i.e., CYP4F2, CYP2C19, APOE, CALU, EPHX1, PROC, CYP2C9, and GGCX) using the SNaPshot assay. Results: The mean daily warfarin dose in patients carrying CYP2C19 rs3814637CC, CYP2C9 rsl057910AA, and GGCX rs699664AA genotype was 3.39, 3.34, and 3.51 mg/ day, respectively, which was higher than those carrying CYP2C19 rs3814637TT, CYP2C9 rsl057910CC, and rs699664GG genotype (2.00, 0.81, and 3.09 mg/day, respectively). Conclusion: These findings indicate that individuals carrying the CYP2C19 rs3814637CC or CYP2C9 rsl057910AA or GGCX rs699664AA genotype needed higher warfarin doses in the Chinese population.