title: Relationship between ABCB1 polymorphisms, thromboelastography and risk of bleeding events in clopidogrel-treated patients with ST-elevation myocardial infarction.
abstract: BACKGROUND
  This study sought to investigate the relationship of polymorphisms in ABCB1 and the predictive value of thromboelastography (TEG) on bleeding risk in clopidogrel-treated patients with ST-elevation myocardial infarction (STEMI).
  
  
  METHODS
  467 consecutive patients with STEMI undergoing percutaneous coronary intervention (PCI) were enrolled. Twenty tag single nucleotide polymorphisms (SNPs) selected from ABCB1 gene and CYP2C19*2, *3, *17 were detected by the ligase detection reaction. Platelet reactivity was assessed by TEG. The follow-up period was 12months.
  
  
  RESULTS
  By receiver operating characteristic curve analysis, the TEG platelet mapping assay value of ADP inhibition had the best predictive value of bleeding academic research consortium definition (BARC) ≥ 3b bleedings, yielding an area under the curve (AUC) of 0.707 (95% CI 0.662-0.749, p=0.009; cut-off value > 93.4%). ADP inhibition can also predict BARC ≥ 3 bleedings with an AUC of 0.594 (95% CI 0.546-0.640, p = 0.05; cut-off value > 92.5%). After adjustment for established risk factors of bleeding including the gain of function CYP2C19*17 allele, age, female gender, renal function, the multivariable logistic regression model demonstrated that ADP inhibition > 92.5% (OR 2.247, 95%CI 1.082-4.665, P=0.03), carriage of rs1045642 (OR 2.943, 95%CI 1.195-7.247, P = 0.019) and rs7779562 (OR 0.453, 95%CI 0.219-0.936, P = 0.032) were independent predictors of BARC ≥ 3 bleedings. These associations were validated in a second cohort of 504 STEMI patients.
  
  
  CONCLUSIONS
  In STEMI patients treated with clopidogrel after PCI, the ABCB1 tag SNP rs1045642 is associated with higher risk of bleedings while rs7779562 is associated with lower bleeding risk, and ADP inhibition in TEG has a predictive value of bleedings.
authors.affiliation: Department of Cardiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 167 Beilishi Road, Xicheng District, Beijing 100037, People's Republic of China.
authors.forename: Jia-Hui
authors.initials: JH
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 167 Beilishi Road, Xicheng District, Beijing 100037, People's Republic of China.
authors.forename: Xiao-Fang
authors.initials: XF
authors.lastname: Tang
authors.affiliation: Department of Cardiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 167 Beilishi Road, Xicheng District, Beijing 100037, People's Republic of China.
authors.forename: Yin
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 167 Beilishi Road, Xicheng District, Beijing 100037, People's Republic of China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Cardiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 167 Beilishi Road, Xicheng District, Beijing 100037, People's Republic of China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Yao
authors.affiliation: Department of Cardiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 167 Beilishi Road, Xicheng District, Beijing 100037, People's Republic of China.
authors.forename: Yuan-Liang
authors.initials: YL
authors.lastname: Ma
authors.affiliation: Department of Cardiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 167 Beilishi Road, Xicheng District, Beijing 100037, People's Republic of China.
authors.forename: Bo
authors.initials: B
authors.lastname: Xu
authors.affiliation: Department of Cardiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 167 Beilishi Road, Xicheng District, Beijing 100037, People's Republic of China.
authors.forename: Run-Lin
authors.initials: RL
authors.lastname: Gao
authors.affiliation: Department of Cardiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 167 Beilishi Road, Xicheng District, Beijing 100037, People's Republic of China.
authors.forename: Zhan
authors.initials: Z
authors.lastname: Gao
authors.affiliation: Department of Cardiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 167 Beilishi Road, Xicheng District, Beijing 100037, People's Republic of China.
authors.forename: Jue
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Cardiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 167 Beilishi Road, Xicheng District, Beijing 100037, People's Republic of China.
authors.forename: Lei
authors.initials: L
authors.lastname: Song
authors.affiliation: Department of Cardiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 167 Beilishi Road, Xicheng District, Beijing 100037, People's Republic of China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Cardiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 167 Beilishi Road, Xicheng District, Beijing 100037, People's Republic of China. Electronic address: dr_xianminmeng@163.com.
authors.forename: Xian-Min
authors.initials: XM
authors.lastname: Meng
authors.affiliation: Department of Cardiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 167 Beilishi Road, Xicheng District, Beijing 100037, People's Republic of China. Electronic address: dr_jinqingyuan@163.com.
authors.forename: Jin-Qing
authors.initials: JQ
authors.lastname: Yuan
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics; D000368:Aged; D000077144:Clopidogrel; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced* / Q000453:epidemiology / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy / Q000601:surgery*; D062645:Percutaneous Coronary Intervention / Q000009:adverse effects; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects*; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D013916:Thrombelastography; D013988:Ticlopidine / Q000009:adverse effects / Q000031:analogs & derivatives*
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine
keywords: ABCB1; Clopidogrel; Polymorphisms; Thromboelastography; bleeding