title: Association of PEAR1 genetic variants with platelet reactivity in response to dual antiplatelet therapy with aspirin and clopidogrel in the Chinese patient population after percutaneous coronary intervention.
abstract: BACKGROUND
  Platelet Endothelial Aggregation Receptor-1 (PEAR1) is a recently reported platelet transmembrane protein which plays an important role in platelet aggregation. The aim of this study was to investigate whether PEAR1 genetic variations were associated with platelet reactivity as assessed by adenosine diphosphate(ADP)-induced platelet aggregation in Chinese patients treated with aspirin and clopidogrel.
  
  
  METHODS
  Patients with coronary heart disease (CHD) who underwent percutaneous coronary intervention (PCI) were enrolled in the study. All patients were on dual antiplatelet therapy with aspirin and clopidogrel. ADP-induced platelet aggregation was measured by thromboelastography and defined as percent inhibition of platelet aggregation (IPA). Patients (n=204) with IPA <30% were identified as high on-treatment platelet reactivity (HPR). Patients (n=201) with IPA >70% were identified as low on-treatment platelet reactivity (LPR). Sixteen single nucleotide polymorphisms (SNPs) of PEAR1 were determined by a method of improved multiple ligase detection reaction.
  
  
  RESULTS
  Among the 16 SNPs examined by univariate analysis, 5 SNPs were significantly associated with ADP-induced platelet aggregation. Minor allele C at rs11264580 (p=0.033), minor allele G at rs2644592 (p=0.048), minor allele T at rs3737224 (p=0.033) and minor allele T at rs41273215 (p=0.025) were strongly associated with HPR, whereas homozygous TT genotype at rs57731889 (p=0.009) was associated with LPR. Multivariate logistic regression analysis further revealed that the minor allele T at rs41273215 (p=0.038) was an independent predictor of HPR and the homozygous TT genotype at rs57731889 (p=0.003) was an independent predictor of LPR.
  
  
  CONCLUSIONS
  PEAR1 genetic variations were strongly associated with ADP-induced platelet aggregation in Chinese patients with CHD treated with aspirin and clopidogrel. These genetic variations may contribute to the variability in platelet function. The utility of PEAR1 genetic variants in the assessment and prediction of cardiovascular risk warrants further investigation.
authors.affiliation: State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beilishi Road No. 167, Xicheng District, Beijing 100037, People's Republic of China; Peking Union Medical College, Beijing 100037, People's Republic of China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Yao
authors.affiliation: State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beilishi Road No. 167, Xicheng District, Beijing 100037, People's Republic of China; Peking Union Medical College, Beijing 100037, People's Republic of China.
authors.forename: Xiao-Fang
authors.initials: XF
authors.lastname: Tang
authors.affiliation: State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beilishi Road No. 167, Xicheng District, Beijing 100037, People's Republic of China; Peking Union Medical College, Beijing 100037, People's Republic of China.
authors.forename: Jia-Hui
authors.initials: JH
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beilishi Road No. 167, Xicheng District, Beijing 100037, People's Republic of China; Peking Union Medical College, Beijing 100037, People's Republic of China.
authors.forename: Chen
authors.initials: C
authors.lastname: He
authors.affiliation: State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beilishi Road No. 167, Xicheng District, Beijing 100037, People's Republic of China; Peking Union Medical College, Beijing 100037, People's Republic of China.
authors.forename: Yuan-Liang
authors.initials: YL
authors.lastname: Ma
authors.affiliation: State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beilishi Road No. 167, Xicheng District, Beijing 100037, People's Republic of China; Peking Union Medical College, Beijing 100037, People's Republic of China.
authors.forename: Jing-Jing
authors.initials: JJ
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beilishi Road No. 167, Xicheng District, Beijing 100037, People's Republic of China; Peking Union Medical College, Beijing 100037, People's Republic of China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Song
authors.affiliation: State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beilishi Road No. 167, Xicheng District, Beijing 100037, People's Republic of China; Peking Union Medical College, Beijing 100037, People's Republic of China.
authors.forename: Ru
authors.initials: R
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beilishi Road No. 167, Xicheng District, Beijing 100037, People's Republic of China; Peking Union Medical College, Beijing 100037, People's Republic of China.
authors.forename: Xian-Min
authors.initials: XM
authors.lastname: Meng
authors.affiliation: State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beilishi Road No. 167, Xicheng District, Beijing 100037, People's Republic of China; Peking Union Medical College, Beijing 100037, People's Republic of China.
authors.forename: Lei
authors.initials: L
authors.lastname: Song
authors.affiliation: State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beilishi Road No. 167, Xicheng District, Beijing 100037, People's Republic of China; Peking Union Medical College, Beijing 100037, People's Republic of China.
authors.forename: Jue
authors.initials: J
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beilishi Road No. 167, Xicheng District, Beijing 100037, People's Republic of China; Peking Union Medical College, Beijing 100037, People's Republic of China.
authors.forename: Miao
authors.initials: M
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beilishi Road No. 167, Xicheng District, Beijing 100037, People's Republic of China; Peking Union Medical College, Beijing 100037, People's Republic of China.
authors.forename: Bo
authors.initials: B
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beilishi Road No. 167, Xicheng District, Beijing 100037, People's Republic of China; Peking Union Medical College, Beijing 100037, People's Republic of China.
authors.forename: Run-Lin
authors.initials: RL
authors.lastname: Gao
authors.affiliation: State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beilishi Road No. 167, Xicheng District, Beijing 100037, People's Republic of China; Peking Union Medical College, Beijing 100037, People's Republic of China. Electronic address: dr_jinqingyuan@sina.com.
authors.forename: Jin-Qing
authors.initials: JQ
authors.lastname: Yuan
mesh_terms: D000368:Aged; D044466:Asian People / Q000235:genetics; D001241:Aspirin / Q000627:therapeutic use*; D001792:Blood Platelets / Q000187:drug effects; D002681:China / Q000453:epidemiology; D000077144:Clopidogrel; D003327:Coronary Disease / Q000453:epidemiology / Q000235:genetics / Q000601:surgery / Q000628:therapy*; D005260:Female; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D062645:Percutaneous Coronary Intervention / Q000379:methods; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D020641:Polymorphism, Single Nucleotide; D011956:Receptors, Cell Surface / Q000235:genetics*; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: C502809:PEAR1 protein, human; D010975:Platelet Aggregation Inhibitors; D011956:Receptors, Cell Surface; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin
keywords: Aspirin; Clopidogrel; Genetic variants; Platelet endothelial aggregation receptor 1; Platelet reactivity