title: Effects of coexisting polymorphisms of CYP2C19 and P2Y12 on clopidogrel responsiveness and clinical outcome in patients with acute coronary syndromes undergoing stent-based coronary intervention.
abstract: BACKGROUND
  The CYP2C19 G681A single polymorphism has been proven to affect clopidogrel responsiveness. However, the effect of coexisting polymorphisms of other genes has not yet been reported in the Chinese population. This study investigated the effect of coexisting polymorphisms of CYP2C19 and P2Y12 on clopidogrel responsiveness and adverse clinical events in Chinese patients.
  
  
  METHODS
  In 577 Han Chinese patients undergoing stent placement because of acute coronary syndrome had platelet reactivity assessed by thromboelastography, and the CYP2C19 G681A and P2Y12 C34T polymorphisms were detected by the ligase detection reaction. Primary clinical endpoints included cardiovascular death, nonfatal myocardial infarction, target vessel revascularization, and stent thrombosis. The secondary clinical endpoints were thrombolysis in myocardial infarction bleeding. The follow-up period was 12 months.
  
  
  RESULTS
  Genotyping revealed 194 carriers of the wild type GG genotype of CYP2C19 and the wild type CC genotype of P2Y12 (group 1), 102 carriers of the wild type GG genotype of CYP2C19 and the mutational T allele of P2Y12 (group 2), 163 carriers of the mutational A allele of CYP2C19 and the wild type CC genotype of P2Y12 (group 3), and 118 carriers of the mutational A allele of CYP2C19 and the mutational T allele of P2Y12 (group 4). Group 4 had the lowest ADP-inhibition (49.74 ± 32.61) and the highest prevalence of clopidogrel low response (29.7%) of the four groups. The rate of the composite of primary clinical endpoints increased more in group 4 (8.5%) than in the other three groups; the rate of composite primary endpoints in group 2 (2.9%) and group 3 (3.7%) were not significantly different than that of group 1 (1.5%).
  
  
  CONCLUSIONS
  Coexisting polymorphisms of different genes affected clopidogrel responsiveness and clinical outcome more than single polymorphism in Chinese patients with acute coronary syndrome undergoing percutaneous coronary intervention.
authors.affiliation: Department of Cardiology, Fu Wai Hospital and Cardiovascular Institute, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China.
authors.forename: Xiao-Fang
authors.initials: XF
authors.lastname: Tang
authors.forename: Jia-Hui
authors.initials: JH
authors.lastname: Zhang
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.forename: Ya-Ling
authors.initials: YL
authors.lastname: Han
authors.forename: Bo
authors.initials: B
authors.lastname: Xu
authors.forename: Shu-Bin
authors.initials: SB
authors.lastname: Qiao
authors.forename: Yong-Jian
authors.initials: YJ
authors.lastname: Wu
authors.forename: Jue
authors.initials: J
authors.lastname: Chen
authors.forename: Yuan
authors.initials: Y
authors.lastname: Wu
authors.forename: Ji-Lin
authors.initials: JL
authors.lastname: Chen
authors.forename: Run-Lin
authors.initials: RL
authors.lastname: Gao
authors.forename: Yue-Jin
authors.initials: YJ
authors.lastname: Yang
authors.forename: Jin-Qing
authors.initials: JQ
authors.lastname: Yuan
mesh_terms: D054058:Acute Coronary Syndrome / Q000188:drug therapy* / Q000235:genetics*; D000368:Aged; D000483:Alleles; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D000077144:Clopidogrel; D065731:Cytochrome P-450 CYP2C19; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D011110:Polymorphism, Genetic / Q000235:genetics*; D058925:Receptors, Purinergic P2Y12 / Q000235:genetics*; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: C548576:P2RY12 protein, human; D058925:Receptors, Purinergic P2Y12; D000077144:Clopidogrel; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D013988:Ticlopidine