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A Pharmacogenetics-Based Warfarin Maintenance Dosing Algorithm from Northern Chinese Patients

Author

Listed:
  • Jinxing Chen
  • Liying Shao
  • Ling Gong
  • Fang Luo
  • Jin'e Wang
  • Yi Shi
  • Yu Tan
  • Qianlong Chen
  • Yu Zhang
  • Rutai Hui
  • Yibo Wang

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

Suggested Citation

  • Jinxing Chen & Liying Shao & Ling Gong & Fang Luo & Jin'e Wang & Yi Shi & Yu Tan & Qianlong Chen & Yu Zhang & Rutai Hui & Yibo Wang, 2014. "A Pharmacogenetics-Based Warfarin Maintenance Dosing Algorithm from Northern Chinese Patients," PLOS ONE, Public Library of Science, vol. 9(8), pages 1-9, August.
    • Handle: RePEc:plo:pone00:0105250
    DOI: 10.1371/journal.pone.0105250
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