title: The VKORC1 and CYP2C9 genotypes significantly effect Vitamin K antagonist dosing only in patients over the age of 20years.
abstract: Given the qualitative differences in the role of VKORC1 and CYP2C9 polymorphisms in Vitamin K antagonists (VKA) dosing variation between adults and children, we were interested in determining at what age these polymorphism begin to play a more significant role.
  
  
  
  A prospective cohort study of 190 patients aged 1-86years receiving VKA for treatment of venous thromboembolism. Blood samples were collected beyond the acute thrombotic event when patients were on stable targeted INR (2-3) for plasma testing and VKORC1/CYP2C9 genotyping. Patient demographics including VKA dose were collected. Simple and multiple linear regression was used to assess the relationship of VKA dose with polymorphisms and weight, adjusted for quality of anticoagulation (INR, D-Dimer), liver (AST, ALT) and renal function.
  
  
  
  In subjects 1-19years of age, weight explained 39.0% of dosing variation with VKORC1 and CYP2C9 playing a minor role. In contrast, in subjects 20-40years weight contributed 23%, VKORC1 44% and CYPC29 49% of the VKA dose variation.
  
  
  
  Until the age of 19, weight has a far greater effect on VKA dosing variation than VKORC1 and CYP2C9 polymorphisms. During the age of 20-40years, VKORC1 and CYP2C9 play a significant role.
authors.affiliation: Institute of Clinical Chemistry, Univ. Hospital Kiel & Lübeck, Germany.
authors.forename: U
authors.initials: U
authors.lastname: Nowak-Göttl
authors.affiliation: University of Alberta, Edmonton, Canada.
authors.forename: K
authors.initials: K
authors.lastname: Dietrich
authors.affiliation: Department of Pediatric Hematology/Oncology, Univ. Children Hospital Münster, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Kruempel
authors.affiliation: DRK Blood Center Baden-Wuerttemberg - Hessen, Institute of Transfusion Medicine and Immunohematology Frankfurt/Main, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Geisen
authors.affiliation: University of Alberta, Edmonton, Canada. Electronic address: lesley.mitchell@ualberta.ca.
authors.forename: L G
authors.initials: LG
authors.lastname: Mitchell
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000008:administration & dosage / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D065729:Cytochrome P-450 CYP2C9 / Q000235:genetics*; D054796:Drug Dosage Calculations; D005260:Female; D005838:Genotype; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D054556:Venous Thromboembolism / Q000188:drug therapy* / Q000235:genetics; D014812:Vitamin K / Q000037:antagonists & inhibitors*; D064417:Vitamin K Epoxide Reductases / Q000235:genetics*; D055815:Young Adult
chemical_list: D000925:Anticoagulants; D014812:Vitamin K; D065729:Cytochrome P-450 CYP2C9; C578523:VKORC1 protein, human; D064417:Vitamin K Epoxide Reductases
keywords: Children; Dosage; Genetic polymorphisms; Vitamin K antagonists