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

PLoS One. 2014 Aug 15;9(8):e105250. doi: 10.1371/journal.pone.0105250. eCollection 2014.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Algorithms
  • Anticoagulants / administration & dosage*
  • China
  • Cytochrome P-450 CYP2C9 / genetics*
  • Drug Administration Schedule
  • Female
  • Humans
  • Maintenance Chemotherapy
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Vitamin K Epoxide Reductases / genetics*
  • Warfarin / administration & dosage*

Substances

  • Anticoagulants
  • Warfarin
  • CYP2C9 protein, human
  • Cytochrome P-450 CYP2C9
  • VKORC1 protein, human
  • Vitamin K Epoxide Reductases

Grants and funding

The study was supported by National Natural Science Foundation of China with grants 81322002, 31171220, and 81270333, and the Fundamental Research Funds for the Central Universities with grant 2013-GZ15-YP to Dr. Wang. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.