title: Impact of CYP2C19 gene polymorphism on warfarin maintenance doses in patients with non-valvular atrial fibrillation.
abstract: BACKGROUND
  Pharmacogenetics has provided compelling evidence towards the influence of gene polymorphisms on warfarin therapies. This study aimed to determine the impact of CYP2C19 gene polymorphism on warfarin maintenance doses in patients with non-valvular atrial fibrillation for the progress in overcoming obstacles facing warfarin pharmacogenetics.
  
  
  METHODS
  In this study, we utilized polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) to investigate the distribution of CYP2C19*2 and *3 gene polymorphism in patients with NVAF. In order to exclude the interference of basic indexes, we compared the association between different genotypes and warfarin maintenance doses. And the comparisons among extensive metabolizer, intermediate metabolizer and poor metabolizer were performed.
  
  
  RESULTS
  CYP2C19 mutation accounted for 88.07% of in total NVAF patients, which was 7.38 times of CYP2C19*1/*1 (11.93%). No significant association was observed between different genotypes and basic indexes. The warfarin maintenance dose of patients with CYP2C19*1/*1 was significantly higher than those with other five genotypes (all P<0.05). Besides, the warfarin maintenance doses of patients with CYP2C19*1/*2 and *1/*3 were remarkably higher than those with *2/*2 and *2/*3 (P<0.05). The warfarin maintenance doses of patients with extensive metabolizer were dramatically higher than those with intermediate metabolizer and poor metabolizer (both P<0.05), and also the patients with intermediate metabolizer had higher warfarin maintenance doses than those with poor metabolizer (P<0.05).
  
  
  CONCLUSIONS
  CYP2C19 gene polymorphism can affect maintenance dose of warfarin, with the amount of warfarin dose ranked among different genotypes as follow: CYP2C19*2/*2, CYP2C19*2/*3 and CYP2C19*3/*3<CYP2C19*1/*2 and CYP2C19*1*<CYP2C19*1/*1.
authors.affiliation: Department of Cardiology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, 441021, PR China.
authors.forename: Hongshen
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, 441021, PR China.
authors.forename: Kezhong
authors.initials: K
authors.lastname: Ma
authors.affiliation: Department of Cardiology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, 441021, PR China.
authors.forename: Wenwei
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Cardiology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, 441021, PR China.
authors.forename: Feng
authors.initials: F
authors.lastname: Yang
authors.affiliation: Department of Cardiology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, 441021, PR China.
authors.forename: Jianfei
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Cardiology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, 441021, PR China. Electronic address: Zhou_xyzxyy@126.com.
authors.forename: Hanyun
authors.initials: H
authors.lastname: Zhou
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D001281:Atrial Fibrillation / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics*; D065731:Cytochrome P-450 CYP2C19 / Q000235:genetics*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D060005:Genotyping Techniques; D006801:Humans; D060046:Maintenance Chemotherapy; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D014859:Warfarin / Q000627:therapeutic use*
chemical_list: D014859:Warfarin; D065731:Cytochrome P-450 CYP2C19
keywords: CYP2C19; Extensive metabolizer; Gene polymorphism; Intermediate metabolizer; Non-valvular atrial fibrillation; Poor metabolizer; Warfarin