The impact of age and CYP2C9 and VKORC1 variants on stable warfarin dose in the paediatric population

Br J Haematol. 2014 Jun;165(6):832-5. doi: 10.1111/bjh.12817. Epub 2014 Mar 6.

Abstract

The influence of genetic variation on warfarin dose requirement is limited for paediatric patients. We performed a retrospective, cross-sectional study to examine the effect of variant CYP2C9 and VKORC1 genotypes on warfarin dose in 100 children. Those with VKORC1 genotype AA required 48% of the dose of homozygous wild-type (GG, P < 0·0001). Patients with any variant CYP2C9 allele required 71% of the dose for wild-type (P = 0·001). The effect of variant VKORC1 alleles tended to vary with age, suggesting developmental ontogeny may influence warfarin sensitivity. Age, CYP2C9 genotype, VKORC1 genotype and age:VKORC1 interaction accounted for 53% of warfarin dose variability.

Keywords: CYP2C9; VKORC1; paediatrics; pharmacogenomics; warfarin.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Age Factors
  • Alleles
  • Anticoagulants / administration & dosage*
  • Aryl Hydrocarbon Hydroxylases / genetics*
  • Child
  • Child, Preschool
  • Cross-Sectional Studies
  • Cytochrome P-450 CYP2C9
  • Genetic Variation*
  • Genotype
  • Humans
  • Infant
  • Pharmacogenetics
  • Retrospective Studies
  • Vitamin K Epoxide Reductases / genetics*
  • Warfarin / administration & dosage*

Substances

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