title: [Distribution of variant alleles association with warfarin pharmacokinetics and pharmacodynamics in the Han population in China].
abstract: OBJECTIVE
  To investigate distribution of CYP2C9, CYP3A4, VKORC1 and GGCX gene polymorphisms in the Han  population of Guangdong.
  
  
  METHODS
  The subjects included were 970 Chinese Han patients who received long-term  warfarin anticoagulant therapy orally after valve replacement in Guangdong General Hospital between 2000 and  2008. By selecting and analyzing the 12 single nucleotide polymorphisms (SNPs) loci, rs12572351 G>A, rs9332146  G>A, rs4917639 G>T, rs1057910 A>C (CYP2C9*3), rs1934967 G>T, rs1934968 G>A, rs2242480 T>C, rs2246709 G>A,  rs9923231 C>T (VKORC1-1639 G>A), rs2359612 G>A (VKORC1*2), rs10871454 C>T, and rs699664 T>C, in 4 genes  including CYP2C9, CYP3A4, VKORC1 and GGCX that were possibly correlated with warfarin pharmacodynamics and  pharmacokinetics through literature retrieval, the distribution of mutation frequencies of the 12 SNPs loci in  Chinese Han population were obtained systematically. SNaPshot technique was used to detect gene SNPs, Hardy-Weinberg genetic equilibrium test was used to test population representativeness.
  
  
  RESULTS
  The allelic mutation  frequency at CYP2C9 gene rs12572351 G>A, rs9332146 G>A, rs4917639 C>A, rs1057910 A>C (*3), rs1934967 G>T and  rs1934968 G>A loci was 32.53%, 2.16%, 8.25%, 3.61%, 19.18% and 37.37%, respectively; the allelic mutation  frequency at CYP3A4 gene rs2242480 T>C and rs2246709 G>A loci was 29.07% and 40.41%, respectively; the allelic  mutation frequency at VKORC1 gene rs9923231 C>T, rs2359612 G>A and rs10871454 C>T SNPs loci was 87.99%, 87.94%  and 91.34%, respectively; the allelic mutation frequency at GGCX gene rs699664 T>C locus was 31.86%.
  
  
  CONCLUSIONS
  It is of important clinical significance in individualized warfarin therapy to systematically study distribution  of mutation frequencies at 12 polymorphisms loci in 4 genes including  CYP2C9, CYP3A4 , VKORC1 and GGCX related  to warfarin pharmacodynamics and pharmacokinetics in the Chinese Han population receiving valve replacement.
authors.affiliation: Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Liu
authors.forename: Shi-long
authors.initials: SL
authors.lastname: Zhong
authors.forename: Min
authors.initials: M
authors.lastname: Yang
authors.forename: Hong-hong
authors.initials: HH
authors.lastname: Tan
authors.forename: Hong-wen
authors.initials: HW
authors.lastname: Fei
authors.forename: Ji-yan
authors.initials: JY
authors.lastname: Chen
authors.forename: Xi-yong
authors.initials: XY
authors.lastname: Yu
authors.forename: Shu-guang
authors.initials: SG
authors.lastname: Lin
mesh_terms: D000328:Adult; D000483:Alleles; D000925:Anticoagulants / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000627:therapeutic use; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D002681:China / Q000208:ethnology; D065729:Cytochrome P-450 CYP2C9; D051544:Cytochrome P-450 CYP3A / Q000235:genetics; D005260:Female; D006349:Heart Valve Diseases / Q000188:drug therapy / Q000235:genetics / Q000601:surgery; D019918:Heart Valve Prosthesis Implantation; D006801:Humans; D008297:Male; D008875:Middle Aged; D006899:Mixed Function Oxygenases / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011184:Postoperative Period; D064417:Vitamin K Epoxide Reductases; D014859:Warfarin / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D000925:Anticoagulants; D014859:Warfarin; D006899:Mixed Function Oxygenases; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; C578523:VKORC1 protein, human; D064417:Vitamin K Epoxide Reductases