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

Vear SI, Ayers GD, Van Driest SL, Sidonio RF, Stein CM, Ho RH
Br J Haematol. 2014 165 (6): 832-5

PMID: 24601977 · PMCID: PMC4043918 · DOI:10.1111/bjh.12817

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.

© 2014 John Wiley & Sons Ltd.

MeSH Terms (17)

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

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