title: Frequency of CYP2C9 alleles in Koreans and their effects on losartan pharmacokinetics.
abstract: OBJECTIVE
  CYP2C9 enzyme metabolizes numerous clinically important drugs. The aim of this study is to investigate the frequencies of CYP2C9 genotypes and the effects of selected alleles on losartan pharmacokinetics in a large sample of the Korean population.
  
  
  METHODS
  The CYP2C9 gene was genotyped in 1796 healthy Korean subjects. CYP2C9 alleles (CYP2C9*1, *2, *3 and *13 alleles) were measured using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay and direct sequencing assay. The enzymatic activity of each CYP2C9 genotype was evaluated using losartan as the substrate.
  
  
  RESULTS
  The frequencies of CYP2C9*1, *3 and *13 allele were 0.952 (95% confidence interval 0.945-0.959), 0.044 (95% CI 0.037-0.051) and 0.005 (95% CI 0.003-0.007), respectively. The frequencies of the CYP2C9*1/*1, *1/*3, *1/*13 and *3/*3 genotypes were 0.904 (95% CI 0.890-0.918), 0.085 (95% CI 0.072-0.098), 0.009 (95% CI 0.005-0.013) and 0.001 (95% CI 0.000-0.002), respectively. In the pharmacokinetics studies, the AUC(0-∞) of losartan in CYP2C9*3/*3 subjects was 1.42-fold larger than that in CYP2C9*1/*1 subjects, and the AUC(0-∞) of E-3174, a more active metabolite of losartan, in CYP2C9*3/*3 subjects was only 12% of that in CYP2C9*1/*1 subjects.
  
  
  CONCLUSIONS
  The results confirmed the frequencies of CYP2C9 genotypes in a large cohort of Koreans, and detected the CYP2C9*3/*3 genotype. CYP2C9*3/*3 subjects metabolized much less losartan into E-3174 than CYP2C9*1/*1 subjects.
authors.affiliation: School of Pharmacy, Sungkyunkwan University, Suwon, Korea.
authors.forename: Jung-woo
authors.initials: JW
authors.lastname: Bae
authors.forename: Chang-ik
authors.initials: CI
authors.lastname: Choi
authors.forename: Mi-jeong
authors.initials: MJ
authors.lastname: Kim
authors.forename: Da-hee
authors.initials: DH
authors.lastname: Oh
authors.forename: Seul-ki
authors.initials: SK
authors.lastname: Keum
authors.forename: Jung-in
authors.initials: JI
authors.lastname: Park
authors.forename: Bo-hye
authors.initials: BH
authors.lastname: Kim
authors.forename: Hye-kyoung
authors.initials: HK
authors.lastname: Bang
authors.forename: Sung-gon
authors.initials: SG
authors.lastname: Oh
authors.forename: Byung-sung
authors.initials: BS
authors.lastname: Kang
authors.forename: Hyun-joo
authors.initials: HJ
authors.lastname: Park
authors.forename: Hae-deun
authors.initials: HD
authors.lastname: Kim
authors.forename: Ji-hey
authors.initials: JH
authors.lastname: Ha
authors.forename: Hee-jung
authors.initials: HJ
authors.lastname: Shin
authors.forename: Young-hoon
authors.initials: YH
authors.lastname: Kim
authors.forename: Han-sung
authors.initials: HS
authors.lastname: Na
authors.forename: Myeon-woo
authors.initials: MW
authors.lastname: Chung
authors.forename: Choon-gon
authors.initials: CG
authors.lastname: Jang
authors.forename: Seok-yong
authors.initials: SY
authors.lastname: Lee
mesh_terms: D000328:Adult; D000483:Alleles; D000959:Antihypertensive Agents / Q000097:blood*; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D044466:Asian People / Q000235:genetics*; D065729:Cytochrome P-450 CYP2C9; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007093:Imidazoles / Q000097:blood; D019808:Losartan / Q000097:blood*; D008297:Male; D013777:Tetrazoles / Q000097:blood; D055815:Young Adult
chemical_list: D000959:Antihypertensive Agents; D007093:Imidazoles; D013777:Tetrazoles; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; C066026:losartan carboxylic acid; D019808:Losartan