title: Association of P2Y12 gene promoter DNA methylation with the risk of clopidogrel resistance in coronary artery disease patients.
abstract: BACKGROUND
  Clopidogrel inhibits the ADP receptor P2Y12 to keep down the platelet aggregation. The goal of our study is to investigate the contribution of P2Y12 promoter DNA methylation to the risk of clopidogrel resistance (CR).
  
  
  METHODS
  The platelet functions were measured by the VerifyNow P2Y12 assay. Applying the bisulfite pyrosequencing technology, DNA methylation levels of two CpG dinucleotides on P2Y12 promoter were tested among 49 CR cases and 57 non-CR controls. We also investigated the association among P2Y12 DNA methylation, various biochemical characteristics, and CR.
  
  
  RESULTS
  Lower methylation of two CpGs indicated the poorer clopidogrel response (CpG1, P=0.009; CpG2, P=0.022) in alcohol abusing status. Meanwhile CpG1 methylation was inversely correlated with CR in smoking patients (P=0.026) and in subgroup of Albumin<35 (P=0.002). We observed that the level of DNA methylation might be affected by some clinical markers, such as TBIL, LEVF, Albumin, AST. The results also showed that the quantity of stent, fasting blood-glucose, and lower HbAC1 were the predictors of CR.
  
  
  CONCLUSIONS
  The evidence from our study indicates that P2Y12 methylation may bring new hints to elaborate the pathogenesis of CR.
authors.affiliation: Department of Cardiology, The Affiliated Ningbo No. 1 Hospital, School of Medicine, Ningbo University, Ningbo, Zhejiang 315010, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Su
authors.affiliation: Department of Cardiology, The Affiliated Ningbo No. 1 Hospital, School of Medicine, Ningbo University, Ningbo, Zhejiang 315010, China.
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Traditional Chinese Internal Medicine, The Affiliated Ningbo No. 1 Hospital, School of Medicine, Ningbo University, Ningbo, Zhejiang, China.
authors.forename: Qinglin
authors.initials: Q
authors.lastname: Yu
authors.affiliation: The Key Laboratory of Molecular Medicine, The Affiliated Ningbo No. 1 Hospital, School of Medicine, Ningbo University, Ningbo, Zhejiang, China.
authors.forename: Yahui
authors.initials: Y
authors.lastname: Liu
authors.affiliation: The Key Laboratory of Molecular Medicine, The Affiliated Ningbo No. 1 Hospital, School of Medicine, Ningbo University, Ningbo, Zhejiang, China.
authors.forename: Yaqing
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology, The Affiliated Ningbo No. 1 Hospital, School of Medicine, Ningbo University, Ningbo, Zhejiang, China.
authors.forename: Haojun
authors.initials: H
authors.lastname: Song
authors.affiliation: Department of Cardiology, The Affiliated Ningbo No. 1 Hospital, School of Medicine, Ningbo University, Ningbo, Zhejiang 315010, China.
authors.forename: Hanbin
authors.initials: H
authors.lastname: Cui
authors.affiliation: Department of Cardiology, The Affiliated Ningbo No. 1 Hospital, School of Medicine, Ningbo University, Ningbo, Zhejiang 315010, China.
authors.forename: Weiping
authors.initials: W
authors.lastname: Du
authors.affiliation: Department of Cardiology, The Affiliated Ningbo No. 1 Hospital, School of Medicine, Ningbo University, Ningbo, Zhejiang 315010, China.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Fei
authors.affiliation: Department of Cardiology, The Affiliated Ningbo No. 1 Hospital, School of Medicine, Ningbo University, Ningbo, Zhejiang 315010, China.
authors.forename: Junsong
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Cardiology, The Affiliated Ningbo No. 1 Hospital, School of Medicine, Ningbo University, Ningbo, Zhejiang 315010, China.
authors.forename: Shaoyi
authors.initials: S
authors.lastname: Lin
authors.affiliation: Department of Cardiology, The Affiliated Ningbo No. 1 Hospital, School of Medicine, Ningbo University, Ningbo, Zhejiang 315010, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Cardiology, The Affiliated Ningbo No. 1 Hospital, School of Medicine, Ningbo University, Ningbo, Zhejiang 315010, China.
authors.forename: Wenyuan
authors.initials: W
authors.lastname: Zheng
authors.affiliation: Department of Cardiology, The Affiliated Ningbo No. 1 Hospital, School of Medicine, Ningbo University, Ningbo, Zhejiang 315010, China.
authors.forename: Jinyan
authors.initials: J
authors.lastname: Zhong
authors.affiliation: Department of Cardiology, The Affiliated Ningbo No. 1 Hospital, School of Medicine, Ningbo University, Ningbo, Zhejiang 315010, China.
authors.forename: Lulu
authors.initials: L
authors.lastname: Zhang
authors.affiliation: The Key Laboratory of Molecular Medicine, The Affiliated Ningbo No. 1 Hospital, School of Medicine, Ningbo University, Ningbo, Zhejiang, China.
authors.forename: Maoqing
authors.initials: M
authors.lastname: Tong
authors.affiliation: Institute of Preventative Medicine, School of Medicine, Ningbo University, Ningbo, Zhejiang, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Cardiology, The Affiliated Ningbo No. 1 Hospital, School of Medicine, Ningbo University, Ningbo, Zhejiang 315010, China.
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Chen
mesh_terms: D000368:Aged; D000077144:Clopidogrel; D003324:Coronary Artery Disease / Q000188:drug therapy* / Q000235:genetics*; D019175:DNA Methylation / Q000187:drug effects / Q000235:genetics*; D004351:Drug Resistance / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic / Q000235:genetics*; D058921:Purinergic P2Y Receptor Antagonists / Q000627:therapeutic use; D058925:Receptors, Purinergic P2Y12 / Q000235:genetics*; D012307:Risk Factors; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D017211:Treatment Failure
chemical_list: C548576:P2RY12 protein, human; D058921:Purinergic P2Y Receptor Antagonists; D058925:Receptors, Purinergic P2Y12; D000077144:Clopidogrel; D013988:Ticlopidine
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