title: Cytochrome P450 CYP 2C19*2 Associated with Adverse 1-Year Cardiovascular Events in Patients with Acute Coronary Syndrome.
abstract: BACKGROUND
  The cytochrome P450 (CYP450) 2C19 681 genotypes affect the antiplatelet activity of clopidogrel. We investigated the correlation of CYP 2C19 681G > A mutation with clopidogrel resistance (CR). Additionally, we studied the effect of CR on clinical prognosis of patients with acute coronary syndrome (ACS).
  
  
  METHODS
  One hundred ten ACS patients undergoing percutaneous coronary intervention, who were followed-up for 1 year, were included in the study. The patients were co-administered aspirin 100 mg/d and clopidogrel 75mg/d following a loading dose of 300 mg. CR was assessed on the basis of polymorphism observed in the CYP2C19 subgroup.
  
  
  RESULTS
  Patients in GG genotype group exhibited greater inhibition of platelet aggregation than patients in GA and AA genotype groups (16.2 ± 10.1%; 10.2 ± 9.9%; 8.0 ± 5.9%, respectively, p < 0.01). CYP2C19 681GG genotype group was associated with lower CR than CYP2C19 681A allele (GA + AA) group (9/59 vs. (12+5)/51; p = 0.009). Over a follow-up of 12 months, the incidence of recurrent angina, acute myocardial infarction, and intra-stent thrombosis in CYP2C19 681 GG carriers was significantly lower than that in CYP2C19 681A allele (GA + AA) group (2/59 vs. 8/51, 1/59 vs. 6/51, 0 vs. 4/51, respectively, p < 0.05).
  
  
  CONCLUSIONS
  CYP 2C19*2 is associated with reduced clopidogrel antiplatelet activity and might be an important marker for poor prognosis of ACS.
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Wannan Medical College, Wuhu, China.
authors.forename: You-Quan
authors.initials: YQ
authors.lastname: Wei
authors.affiliation: Department of Cardiology, The Second People's Hospital of Huangchuan County, Xinyang, China.
authors.forename: Dian-Gang
authors.initials: DG
authors.lastname: Wang
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Wannan Medical College, Wuhu, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Yang
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Wannan Medical College, Wuhu, China.
authors.forename: Heng
authors.initials: H
authors.lastname: Cao
mesh_terms: D065767:Activation, Metabolic / Q000235:genetics; D054058:Acute Coronary Syndrome / Q000188:drug therapy / Q000235:genetics* / Q000601:surgery; D000368:Aged; D000483:Alleles; D000787:Angina Pectoris / Q000453:epidemiology / Q000235:genetics; D001241:Aspirin / Q000627:therapeutic use; D000077144:Clopidogrel; D023903:Coronary Restenosis / Q000453:epidemiology / Q000235:genetics; D003328:Coronary Thrombosis / Q000453:epidemiology / Q000235:genetics; D065731:Cytochrome P-450 CYP2C19 / Q000235:genetics* / Q000502:physiology; D004351:Drug Resistance / Q000235:genetics*; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000453:epidemiology / Q000235:genetics; D062645:Percutaneous Coronary Intervention; D010975:Platelet Aggregation Inhibitors / Q000493:pharmacokinetics* / Q000627:therapeutic use; D020641:Polymorphism, Single Nucleotide; D011355:Prodrugs / Q000493:pharmacokinetics* / Q000627:therapeutic use; D011379:Prognosis; D011446:Prospective Studies; D012008:Recurrence; D015607:Stents; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D010975:Platelet Aggregation Inhibitors; D011355:Prodrugs; D000077144:Clopidogrel; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D013988:Ticlopidine; D001241:Aspirin