Association of genetic polymorphisms with warfarin dose requirements in Chinese patients

Genet Test Mol Biomarkers. 2013 Dec;17(12):932-6. doi: 10.1089/gtmb.2013.0303. Epub 2013 Aug 13.

Abstract

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 rs1057910AA, and GGCX rs699664AA genotype was 3.39, 3.34, and 3.51 mg/day, respectively, which was higher than those carrying CYP2C19 rs3814637TT, CYP2C9 rs1057910CC, 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 rs1057910AA or GGCX rs699664AA genotype needed higher warfarin doses in the Chinese population.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Anticoagulants / administration & dosage*
  • Anticoagulants / pharmacokinetics
  • Aryl Hydrocarbon Hydroxylases / genetics*
  • Asian People*
  • China
  • Cytochrome P-450 CYP2C19
  • Cytochrome P-450 CYP2C9
  • Female
  • Humans
  • Male
  • Polymorphism, Single Nucleotide*
  • Warfarin / administration & dosage*
  • Warfarin / pharmacokinetics

Substances

  • Anticoagulants
  • Warfarin
  • CYP2C9 protein, human
  • Cytochrome P-450 CYP2C9
  • Aryl Hydrocarbon Hydroxylases
  • CYP2C19 protein, human
  • Cytochrome P-450 CYP2C19