CYP2C19 and PON1 polymorphisms regulating clopidogrel bioactivation in Chinese, Malay and Indian subjects

Pharmacogenomics. 2012 Apr;13(5):533-42. doi: 10.2217/pgs.12.24.

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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aryl Hydrocarbon Hydroxylases / genetics*
  • Aryldialkylphosphatase / genetics*
  • Asian People / genetics*
  • China
  • Clopidogrel
  • Cytochrome P-450 CYP2C19
  • Female
  • Gene Frequency
  • Genotype
  • Humans
  • India
  • Malaysia
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Platelet Aggregation / drug effects
  • Platelet Aggregation / genetics
  • Platelet Aggregation Inhibitors / administration & dosage
  • Platelet Aggregation Inhibitors / pharmacokinetics*
  • Platelet Aggregation Inhibitors / pharmacology
  • Platelet Aggregation Inhibitors / therapeutic use
  • Polymorphism, Single Nucleotide*
  • Ticlopidine / administration & dosage
  • Ticlopidine / analogs & derivatives*
  • Ticlopidine / pharmacokinetics
  • Ticlopidine / pharmacology
  • Ticlopidine / therapeutic use
  • White People / genetics*

Substances

  • Platelet Aggregation Inhibitors
  • Clopidogrel
  • Aryl Hydrocarbon Hydroxylases
  • CYP2C19 protein, human
  • Cytochrome P-450 CYP2C19
  • Aryldialkylphosphatase
  • PON1 protein, human
  • Ticlopidine