title: Cytochrome P450 2C9 gene polymorphism and warfarin maintenance dosage in pediatric patients: A systematic review and meta-analysis.
abstract: OBJECTIVE
  To assess the effect of Cytochrome P450 2C9 (CYP2C9) gene polymorphism on pediatric warfarin maintenance dosage requirement.
  
  
  METHODS
  A previously developed search strategy was conducted in PubMed, EMBASE, and the Cochrane Library. Eligible studies published prior to January 27, 2016, were identified and compared against strict inclusion/exclusion criteria. Required data were extracted, and researchers were consulted for additional data if needed. Review Manager version 5.2.3 software was used to analyze the relationship between CYP2C9 polymorphisms and warfarin maintenance doses in pediatric patients. Eight articles with a combined total of 507 pediatric patients were included in the meta-analysis.
  
  
  RESULTS
  Maintenance warfarin doses in patients with CYP2C9 *1/*2 genotype, CYP2C9 *1/*3 genotype, and CYP2C9 variant carriers which contain at least one variant allele (*2 or *3) were from 15% to 41% lower than doses in patients with the wild-type allele (CYP2C9 *1/*1): All differences were significant with P-values <.05. The Fontan procedure as a medical indication for anticoagulation was also associated with a lower warfarin maintenance dose; however, target INR range was not.
  
  
  CONCLUSIONS
  We found that CYP2C9 gene polymorphism (referring to the presence of *1/*2, *1/*3, and variant genotypes in the population in addition to the wild type) was significantly associated with decreased warfarin maintenance dose requirements. Additionally, a specific indication for warfarin, the Fontan procedure, was associated with a lower daily warfarin dose. However, the results of our study require confirmation from more research with larger numbers of pediatric patients.
authors.affiliation: Department of Pharmacy, Fujian Medical University Union Hospital, Fuzhou, China.
authors.forename: Jinhua
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Hematology/Rheumatology, The Second Hospital of Xiamen, Xiamen, China.
authors.forename: Lihong
authors.initials: L
authors.lastname: Tian
authors.affiliation: Fujian Institute of Hematology, Fujian Provincial Key Laboratory on Hematology, Fujian Medical University Union Hospital, Fuzhou, China.
authors.forename: Jinlong
authors.initials: J
authors.lastname: Huang
authors.affiliation: Fujian Institute of Hematology, Fujian Provincial Key Laboratory on Hematology, Fujian Medical University Union Hospital, Fuzhou, China.
authors.forename: Sihan
authors.initials: S
authors.lastname: Huang
authors.affiliation: Fujian Institute of Hematology, Fujian Provincial Key Laboratory on Hematology, Fujian Medical University Union Hospital, Fuzhou, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Chai
authors.affiliation: Fujian Institute of Hematology, Fujian Provincial Key Laboratory on Hematology, Fujian Medical University Union Hospital, Fuzhou, China.
authors.forename: Jianzhen
authors.initials: J
authors.lastname: Shen
mesh_terms: D000293:Adolescent; D000367:Age Factors; D000925:Anticoagulants / Q000008:administration & dosage* / Q000378:metabolism / Q000493:pharmacokinetics; D001777:Blood Coagulation / Q000187:drug effects*; D016009:Chi-Square Distribution; D002648:Child; D002675:Child, Preschool; D065729:Cytochrome P-450 CYP2C9 / Q000235:genetics* / Q000378:metabolism; D054796:Drug Dosage Calculations; D005260:Female; D005838:Genotype; D006801:Humans; D007223:Infant; D019934:International Normalized Ratio; D008297:Male; D010597:Pharmacogenetics; D000071184:Pharmacogenomic Variants; D010641:Phenotype; D011110:Polymorphism, Genetic; D014859:Warfarin / Q000008:administration & dosage* / Q000378:metabolism / Q000493:pharmacokinetics; D055815:Young Adult
chemical_list: D000925:Anticoagulants; D014859:Warfarin; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9
keywords: CYP2C9; Gene polymorphisms; Meta-analysis; Pediatric patients; Systematic review; Warfarin