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

Jinxing Chen,Yi Shi,Yu Tan,Rutai Hui,Yibo Wang,Liying Shao,Qianlong Chen,Yu Zhang,Ling Gong,Jin'E Wang,Fang Luo,Yan Gong

doi:10.1371/journal.pone.0105250

Jinxing Chen, Yi Shi + Show 10 more

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https://doi.org/10.1371/journal.pone.0105250

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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.

Highlights

Warfarin has remained the mainstay of oral anticoagulant therapy for the treatment and prevention of thromboembolism
Many studies have shown that single nucleotide polymorphisms (SNPs) within CYP2C9 and VKORC1 genes are related to warfarin dose requirement [1,2,3,4]
Our algorithm could explain the 45.1% variability of warfarin dose observed in northern Chinese individuals

Summary

Introduction

Warfarin has remained the mainstay of oral anticoagulant therapy for the treatment and prevention of thromboembolism. Many studies have shown that single nucleotide polymorphisms (SNPs) within CYP2C9 (cytochrome P450, family 2, subfamily C, polypeptide 9) and VKORC1 (vitamin K epoxide reductase complex, subunit 1) genes are related to warfarin dose requirement [1,2,3,4]. These two genes in combination with age, gender, and body mass index have been shown to account for 30–50% of the variability in the dosage of warfarin and acenocoumarol [1,4,5,6,7,8,9,10].

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