title: CYP2C19 genotypes and their impact on clopidogrel responsiveness in percutaneous coronary intervention.
abstract: BACKGROUND
  Cytochrome P450 2C19 (CYP2C19) loss-of-function polymorphisms are more common in Asian populations and have been associated with diminished antiplatelet response to clopidogrel. In this era of 'personalised medicine', combining genotyping and phenotyping as a strategy to personalise antiplatelet therapy warrants further exploration.
  
  
  OBJECTIVE
  This study aimed to investigate the prevalence and impact of CYP2C19*2, *3 and *17 genotypes on clopidogrel responsiveness in a multiethnic Malaysian population planned for percutaneous coronary intervention.
  
  
  METHODS
  Between October 2010 and March 2011, a total of 118 consecutive patients planned for percutaneous coronary intervention were enrolled in Sarawak General Hospital, Borneo. All patients received at least 75 mg aspirin daily for at least 2 days and 75 mg clopidogrel daily for at least 4 days prior to angiography.
  
  
  METHODS
  Genotyping for CYP2C19*2 (rs4244285, 681G > A), *3 (rs4986893, 636G > A) and *17 (rs11188072, -3402C > T) alleles were performed by polymerase chain reaction-restriction fragment linked polymorphism method. Whole blood ADP-induced platelet aggregation was assessed with multiple electrode platelet aggregometry (MEA) using the Multiplate Analyzer.
  
  
  METHODS
  The distribution of CYP2C19*2, *3 and *17 among different ethnic groups and the association between genotype, clopidogrel responsiveness and clinical outcome were the main outcome measures.
  
  
  RESULTS
  The highest prevalence of poor metabolisers (carriers of at least one copy of the *2 or *3 allele) was among the Chinese (53.7 %), followed by the Malays (26.9 %), Ibans (16.4 %) and other races (3.0 %). Poor metabolisers (PMs) had the highest mean MEA (303.6 AU*min), followed by normal metabolisers (NMs) with 270.5 AU*min and extensive metabolisers (EMs) with 264.1 AU*min (p = 0.518). Among poor responders to clopidogrel, 65.2 % were PMs and NMs, respectively, whereas none were EMs (p = 0.350). Two cardiac-related deaths were reported.
  
  
  CONCLUSIONS
  There was a diverse inter-ethnic difference in the distribution of CYP2C19 polymorphism. The findings of this study echo that of other studies where genotype appears to have a limited impact on clopidogrel responsiveness and clinical outcome in low-risk patients.
authors: Department of Pharmacy, Sarawak General Hospital Heart Centre, Kota Samarahan, Malaysia. melissamejin@crc.gov.my
authors: Melissa
authors: M
authors: Mejin
authors: Wen Ni
authors: WN
authors: Tiong
authors: Lana Yin Hui
authors: LY
authors: Lai
authors: Lee Len
authors: LL
authors: Tiong
authors: Adam Mohamad
authors: AM
authors: Bujang
authors: Siaw San
authors: SS
authors: Hwang
authors: Tiong Kiam
authors: TK
authors: Ong
authors: Alan Yean Yip
authors: AY
authors: Fong
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D044466:Asian People / Q000235:genetics; D001241:Aspirin / Q000008:administration & dosage; D000077144:Clopidogrel; D065731:Cytochrome P-450 CYP2C19; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D008296:Malaysia; D008297:Male; D008875:Middle Aged; D062645:Percutaneous Coronary Intervention / Q000379:methods*; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D015995:Prevalence; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D013988:Ticlopidine; D001241:Aspirin
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