title: Frequency of CYP2C9 and VKORC1 gene polymorphisms and their influence on warfarin dose in Egyptian pediatric patients.
abstract: BACKGROUND
  Warfarin is a widely used anticoagulant that shows a high inter-individual variability in the dose needed to achieve target anticoagulation. In adults, common genetic variants in the cytochrome P450-2C9 (CYP2C9) and vitamin K epoxide reductase complex (VKORC1) enzymes, in addition to non-genetic factors, explain this dose variability. In children, data about warfarin pharmacogenetics are limited and inconsistent.
  
  
  METHODS
  CYP2C9 (*2 and *3) alleles and the VKORC1 (C1173T and G-1639A) polymorphisms were studied by multiplex real time polymerase chain reaction in 41 pediatric patients who received stable warfarin maintenance dose.
  
  
  RESULTS
  The allele frequency of the studied genes was CYP2C9*2 (0.085), CYP2C9*3 (0.12), VKORC1 1173T (0.52), and VKORC1 -1639A (0.54). In univariate analysis, patients' age, weight, and height were significantly (p < 0.0001) associated with warfarin maintenance dose. However, CYP2C9 and VKORC1 gene polymorphisms did not affect warfarin dose. In multivariate analysis, age was found to be the only significant determinant of daily warfarin maintenance dose (p = 0.045).
  
  
  CONCLUSIONS
  Age was the most significant determinant of warfarin dosage in this preliminary study including Egyptian pediatric patients. Further studies involving larger numbers of children are warranted to determine the true impact of genetic factors on warfarin doses in pediatric patients.
authors.affiliation: Clinical Pathology Department, Kasr Al-Ainy School of Medicine, Cairo University, P.O. Box 99, Manial El-Roda, Cairo, 11553, Egypt.
authors.forename: Mennat-Allah
authors.initials: MA
authors.lastname: Kamal El-Din
authors.forename: Marwa Salah
authors.initials: MS
authors.lastname: Farhan
authors.forename: Randa Ibrahim
authors.initials: RI
authors.lastname: El Shiha
authors.forename: Rania Mohammed Helmy
authors.initials: RM
authors.lastname: El-Kaffas
authors.forename: Somaia Mohammed
authors.initials: SM
authors.lastname: Mousa
mesh_terms: D000925:Anticoagulants / Q000008:administration & dosage*; D002648:Child; D002675:Child, Preschool; D065729:Cytochrome P-450 CYP2C9 / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic; 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; C578523:VKORC1 protein, human; D064417:Vitamin K Epoxide Reductases