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Effect of the VKORC1 genotype on warfarin dose requirements in Japanese pediatric patients

Yuya Kato1, Fukiko Ichida, Kazuyoshi Saito

  • 1Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Japan.

Drug Metabolism and Pharmacokinetics
|January 29, 2011
PubMed

Insights

Vitamin K epoxide reductase complex 1 (VKORC1) genotype significantly impacts warfarin dosing in Japanese children. Younger children and those with specific VKORC1 genotypes require higher warfarin doses for stable anticoagulation.

Area of Science:

  • Pharmacogenomics
  • Pediatric Pharmacology

Background:

  • Warfarin is a widely used anticoagulant.
  • Individual warfarin dose requirements vary significantly.
  • Genetic factors, including VKORC1 and CYP2C9 polymorphisms, are known to influence warfarin efficacy.

Purpose of the Study:

  • To investigate the impact of VKORC1 genotype on warfarin dose requirements in Japanese pediatric patients.
  • To identify key factors influencing warfarin's anticoagulant effect in children.

Main Methods:

  • Study included 48 Japanese pediatric patients on stable warfarin therapy.
  • VKORC1 and CYP2C9 polymorphic alleles were genotyped.
  • Multiple regression analysis evaluated the impact of covariates on warfarin dose and therapeutic prothrombin time-international normalized ratio (PT-INR).

Main Results:

  • VKORC1 genotype and patient age were identified as major determinants of warfarin dose-normalized for body weight.
  • Patients with VKORC1 1173CT or 1173CC genotypes showed a 52.3% reduced anticoagulant effect compared to the 1173TT genotype.
  • The anticoagulant effect of warfarin increased by 10.5% annually in this pediatric cohort.

Conclusions:

  • VKORC1 genotyping is valuable for personalized warfarin therapy in pediatric patients.
  • Younger children require higher weight-normalized warfarin doses.
  • CYP2C9 polymorphism analysis was limited due to a small sample size of specific alleles.

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