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.
authors.affiliation: Department of Pediatrics, Monroe Carell Jr Children's Hospital at Vanderbilt, Nashville, TN, USA.
authors.forename: Susan I
authors.initials: SI
authors.lastname: Vear
authors.forename: Gregory D
authors.initials: GD
authors.lastname: Ayers
authors.forename: Sara L
authors.initials: SL
authors.lastname: Van Driest
authors.forename: Robert F
authors.initials: RF
authors.lastname: Sidonio
authors.forename: Charles Michael
authors.initials: CM
authors.lastname: Stein
authors.forename: Richard H
authors.initials: RH
authors.lastname: Ho
mesh_terms: D000293:Adolescent; D000367:Age Factors; D000483:Alleles; D000925:Anticoagulants / Q000008:administration & dosage*; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D065729:Cytochrome P-450 CYP2C9; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D007223:Infant; D010597:Pharmacogenetics; D012189:Retrospective Studies; D064417:Vitamin K Epoxide Reductases / Q000235:genetics*; D014859:Warfarin / Q000008:administration & dosage*
chemical_list: D000925:Anticoagulants; D014859:Warfarin; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; C578523:VKORC1 protein, human; D064417:Vitamin K Epoxide Reductases
keywords: CYP2C9; VKORC1; paediatrics; pharmacogenomics; warfarin