title: CYP2C19 and PON1 polymorphisms regulating clopidogrel bioactivation in Chinese, Malay and Indian subjects.
abstract: AIM, MATERIALS & METHODS: We investigated the functional significance of CYP2C19*2, *3, *17 and PON1 Q192R SNPs in 89 consecutive Asian patients on clopidogrel treatment and the prevalence of functionally significant polymorphisms among 300 Chinese, Malays and Asian Indians.
  
  
  RESULTS
  Both CYP2C19 loss-of-function alleles (*2 or *3) were associated with higher platelet reactivity while the CYP2C19 gain-of-function allele (*17) had lower platelet reactivity. For PON1, the median PRI was not significantly different between the QQ, QR and RR groups. The allele frequencies of CYP2C19*2, CYP2C19*3 and CYP2C19*17 were 0.280, 0.065 and 0.010 (rare) for Chinese, 0.310, 0.050 and 0.025 for Malays, and 0.375, 0.010 (rare) and 0.165 for Indians, respectively.
  
  
  CONCLUSIONS
  Our data suggest that genotyping studies to investigate clopidogrel response should include CYP2C19*2 and *3 but not *17 polymorphisms in Chinese, and CYP2C19*2 and *17 polymorphisms but not *3 in Indians. All three polymorphisms should preferably be genotyped in Malays.
authors.affiliation: National University Heart Centre, 1E Kent Ridge Road, Singapore 119228, Singapore. mark_chan@nuhs.edu.sg
authors.forename: Mark Y
authors.initials: MY
authors.lastname: Chan
authors.forename: Karen
authors.initials: K
authors.lastname: Tan
authors.forename: Huay-Cheem
authors.initials: HC
authors.lastname: Tan
authors.forename: Pei-Tee
authors.initials: PT
authors.lastname: Huan
authors.forename: Bei
authors.initials: B
authors.lastname: Li
authors.forename: Qian-Hui
authors.initials: QH
authors.lastname: Phua
authors.forename: Hong-Kai
authors.initials: HK
authors.lastname: Lee
authors.forename: Chi-Hang
authors.initials: CH
authors.lastname: Lee
authors.forename: Adrian
authors.initials: A
authors.lastname: Low
authors.forename: Richard C
authors.initials: RC
authors.lastname: Becker
authors.forename: Wen-Chong
authors.initials: WC
authors.lastname: Ong
authors.forename: Mark A
authors.initials: MA
authors.lastname: Richards
authors.forename: Agus
authors.initials: A
authors.lastname: Salim
authors.forename: E-Shyong
authors.initials: ES
authors.lastname: Tai
authors.forename: Evelyn
authors.initials: E
authors.lastname: Koay
mesh_terms: D000368:Aged; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D043303:Aryldialkylphosphatase / Q000235:genetics*; D044466:Asian People / Q000235:genetics*; D002681:China; D000077144:Clopidogrel; D065731:Cytochrome P-450 CYP2C19; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007194:India; D008296:Malaysia; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010974:Platelet Aggregation / Q000187:drug effects / Q000235:genetics; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000627:therapeutic use; D020641:Polymorphism, Single Nucleotide; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D044465:White People / Q000235:genetics*
chemical_list: D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human; D013988:Ticlopidine