title: Associations between P2RY12 gene polymorphisms and risks of clopidogrel resistance and adverse cardiovascular events after PCI in patients with acute coronary syndrome.
abstract: Clopidogrel resistance in patients with acute coronary syndrome (ACS) is one of the key causes of recurrent cardiovascular disease (CVD) events after percutaneous coronary intervention (PCI). Clopidogrel targets the platelet membrane receptor P2RY12 to inhibit platelet aggregation via adenosine diphosphate (ADP). This study aimed to investigate the relationships between P2RY12 polymorphisms and the risk of clopidogrel resistance and adverse CVD events after PCI. From January 2015 to December 2014, patients who had been diagnosed with ACS undergoing PCI and treated with clopidogrel were recruited for this prospective cohort study (N = 498). Data regarding demographics, medication intake, and ACS lesion were recorded, and whole blood samples were collected for biochemical tests, ADP-induced platelet aggregation ratio detection, and P2RY12 genotyping. P2RY12 genotyping was performed by polymerase chain reaction. The left ventricular ejection fraction was calculated by echocardiography. After 3 to 12 months of follow-up, data regarding any adverse CVD event or death were recorded. The allele frequencies for the T variation alleles in C34T and G52T of P2RY12 were 20.3% and 11.6%, respectively. Patients with T variations at C34T or G52T of P2RY12 had a significantly higher risk of clopidogrel resistance (C34T: P < 0.001; G52T: P = 0.003) and total cardiovascular events (C34T: P = 0.013; G52T: P = 0.018) compared to those with the wild-type genotype. Moreover, multivariable logistic regression showed that patients with the T variations in C34T (odds ratio [OR]: 2.89 (95% confidence interval [CI]: 1.48-5.64), P = 0.002) and G52T (OR: 3.68 [95% CI: 1.71-7.92], P = 0.001) also had a significantly higher risk of clopidogrel resistance. Also, the T variations in C34T (OR: 2.68 [95% CI: 1.07-6.73], P = 0.035) and G52T (OR: 5.64 [95% CI: 1.52-20.88], P = 0.010) significantly increased the risk of post-PCI CVD events after accounting for confounding factors. The P2RY12 gene polymorphisms C34T and G52T were significantly associated with a higher risk of clopidogrel resistance and sequential cardiovascular events in Chinese ACS patients after PCI.
authors.affiliation: Department of Cardiovascular Disease, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, PR China.
authors.forename: Miaonan
authors.initials: M
authors.lastname: Li
authors.forename: Hongju
authors.initials: H
authors.lastname: Wang
authors.forename: Ling
authors.initials: L
authors.lastname: Xuan
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Shi
authors.forename: Tong
authors.initials: T
authors.lastname: Zhou
authors.forename: Ningru
authors.initials: N
authors.lastname: Zhang
authors.forename: Yuli
authors.initials: Y
authors.lastname: Huang
mesh_terms: D054058:Acute Coronary Syndrome / Q000517:prevention & control* / Q000601:surgery; D000368:Aged; D000077144:Clopidogrel; D004351:Drug Resistance / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D062645:Percutaneous Coronary Intervention / Q000009:adverse effects; D058921:Purinergic P2Y Receptor Antagonists / Q000627:therapeutic use*; D058925:Receptors, Purinergic P2Y12 / Q000235:genetics*; D055502:Secondary Prevention; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: C548576:P2RY12 protein, human; D058921:Purinergic P2Y Receptor Antagonists; D058925:Receptors, Purinergic P2Y12; D000077144:Clopidogrel; D013988:Ticlopidine