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A pharmacogenetics-based warfarin maintenance dosing algorithm from Northern Chinese patients.


ABSTRACT: Inconsistent associations with warfarin dose were observed in genetic variants except VKORC1 haplotype and CYP2C9*3 in Chinese people, and few studies on warfarin dose algorithm was performed in a large Chinese Han population lived in Northern China. Of 787 consenting patients with heart-valve replacements who were receiving long-term warfarin maintenance therapy, 20 related Single nucleotide polymorphisms were genotyped. Only VKORC1 and CYP2C9 SNPs were observed to be significantly associated with warfarin dose. In the derivation cohort (n?=?551), warfarin dose variability was influenced, in decreasing order, by VKORC1 rs7294 (27.3%), CYP2C9*3(7.0%), body surface area(4.2%), age(2.7%), target INR(1.4%), CYP4F2 rs2108622 (0.7%), amiodarone use(0.6%), diabetes mellitus(0.6%), and digoxin use(0.5%), which account for 45.1% of the warfarin dose variability. In the validation cohort (n?=?236), the actual maintenance dose was significantly correlated with predicted dose (r?=?0.609, P<0.001). Our algorithm could improve the personalized management of warfarin use in Northern Chinese patients.

SUBMITTER: Chen J 

PROVIDER: S-EPMC4134280 | BioStudies | 2014-01-01

REPOSITORIES: biostudies

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