title: Associations of P2Y12R gene polymorphisms with susceptibility to coronary heart disease and clinical efficacy of antiplatelet treatment with clopidogrel.
abstract: OBJECTIVE
  To investigate the correlations of three P2Y12 receptor (P2Y12R) gene polymorphisms (rs7428575 T>G, rs2046934 C>T, and rs3732759 A>G) with susceptibility to coronary artery disease (CHD) and clinical efficacy of clopidogrel treatment for CHD.
  
  
  METHODS
  From May 2014 to May 2015, 178 CHD patients (the case group) and 182 healthy controls (the control group) were selected from our hospital. The platelet-rich plasma (PRP) turbidimetry was used to measure the rate of adenosine diphosphate (ADP)-induced platelet aggregation before and after clopidogrel treatment. Clopidogrel-sensitive group was defined as a 10% or greater decrease in the rate of platelet aggregation after 10 days of clopidogrel treatment, while clopidogrel-resistant group was defined as a <10% decrease. Genotyping was performed by denaturing high-performance liquid chromatography (DHPLC). A haplotype analysis of P2Y12R gene polymorphisms was performed using SHEsis software.
  
  
  RESULTS
  There were significant differences in genotype and allele frequencies of rs2046934 C>T and rs3732759 A>G between the case and control groups (all P<.05). Haplotypes GTA and TTA were negatively associated with CHD risk (both P<.05), but haplotype TCA was positively associated with CHD risk (P=.005). CHD patients in the clopidogrel-sensitive group had higher frequencies of TT genotype of rs2046934 C>T and lower frequencies of GG genotype of rs3732759 A>G than those in the clopidogrel-resistant group (both P<.05).
  
  
  CONCLUSIONS
  P2Y12R gene rs2046934 C>T and rs3732759 A>G polymorphisms might be associated with the risk of CHD and the efficacy of clopidogrel treatment for CHD.
authors: Department of Cardiology, Henan Provincial People's Hospital, Zhengzhou, Henan, China.
authors: Hong-Hui
authors: HH
authors: Yang
authors: Department of Cardiology, Henan Provincial People's Hospital, Zhengzhou, Henan, China.
authors: Yan
authors: Y
authors: Chen
authors: Department of Cardiology, Henan Provincial People's Hospital, Zhengzhou, Henan, China.
authors: Chuan-Yu
authors: CY
authors: Gao
mesh_terms: D000368:Aged; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D016022:Case-Control Studies; D002851:Chromatography, High Pressure Liquid; D000077144:Clopidogrel; D003327:Coronary Disease / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics*; D004351:Drug Resistance; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D010597:Pharmacogenetics; D010641:Phenotype; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D010979:Platelet Function Tests; D020641:Polymorphism, Single Nucleotide; D058925:Receptors, Purinergic P2Y12 / Q000097:blood / Q000187:drug effects* / Q000235:genetics*; D012307:Risk Factors; D013988:Ticlopidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: C548576:P2RY12 protein, human; D010975:Platelet Aggregation Inhibitors; D058925:Receptors, Purinergic P2Y12; D000077144:Clopidogrel; D013988:Ticlopidine
keywords: 
  P2Y12R
  ; Clopidogrel; Coronary heart disease; Efficacy; Gene polymorphisms; Susceptibility