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

Susan I. Vear; Gregory D. Ayers; Sara L. Van Driest; Robert F. Sidonio; Charles Michael Stein; Richard H. Ho

doi:10.1111/bjh.12817

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

Susan I. Vear
, Gregory D. Ayers
, Sara L. Van Driest
, Robert F. Sidonio
, Charles Michael Stein
, Richard H. Ho

Research output: Contribution to journal › Article › peer-review

26 Scopus citations

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.

Original language	English
Pages (from-to)	832-835
Number of pages	4
Journal	British Journal of Haematology
Volume	165
Issue number	6
DOIs	https://doi.org/10.1111/bjh.12817
State	Published - Jun 2014

Keywords

CYP2C9
Paediatrics
Pharmacogenomics
VKORC1
Warfarin

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10.1111/bjh.12817

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

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, Paediatrics, Pharmacogenomics, VKORC1, Warfarin",

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AU - Vear, Susan I.

AU - Ayers, Gregory D.

AU - Van Driest, Sara L.

AU - Sidonio, Robert F.

AU - Stein, Charles Michael

AU - Ho, Richard H.

PY - 2014/6

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AB - 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.

KW - CYP2C9

KW - Paediatrics

KW - Pharmacogenomics

KW - VKORC1

KW - Warfarin

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

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Keywords

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