Study of the Association of PEAR1, P2Y12, and UGT2A1 Polymorphisms with Platelet Reactivity in Response to Dual Antiplatelet Therapy in Chinese Patients

Cardiology. 2018;140(1):21-29. doi: 10.1159/000488101. Epub 2018 Apr 10.

Abstract

Objectives: Genetic variation is thought to contribute to considerable interindividual variability in platelet function, and there is a pressing need to identify genetic markers that can be used to predict the response to treatment. Our study investigated whether PEAR1, P2Y12, and UGT2A1 polymorphisms were associated with platelet reactivity in response to dual antiplatelet therapy in Chinese patients with acute coronary syndrome.

Methods: Patients with inhibition of platelet aggregation (IPA) < 30% after treatment were classified as the high platelet reactivity (HPR) group. Patients with IPA > 30% were classified as the normal platelet reactivity (NPR) group. ADP-induced platelet aggregation was measured by thromboelastography (TEG) platelet-mapping assay. Thirteen single nucleotide polymorphisms (SNPs) of PEAR1, P2Y12 and UGT2A1 were genotyped using the Mass-ARRAY platform.

Results: Seven SNPs were significantly associated with ADP-induced platelet aggregation by univariate analysis. Major allele G at rs12041331, minor allele G at rs2644592, minor allele C at rs11264580, and minor allele C at rs11249454 were significantly associated with HPR, whereas minor allele T at rs57731889, minor allele A at rs16863356, and minor allele T at rs7634096 were significantly associated with NPR. The mean IPA was significantly lower in patients suffering recurrent ischemic events than in patients without recurrent events in our study (p = 0.048).

Conclusions: Our findings suggest that PEAR1, P2Y12, and UGT2A1 genetic variants may be potential biomarkers that can be used to guide clinical applications of clopidogrel and aspirin in Chinese patients.

Keywords: Acute coronary syndrome; Dual antiplatelet therapy; Genetic variants; Platelet reactivity; Thromboelastography.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Coronary Syndrome / drug therapy*
  • Acute Coronary Syndrome / genetics
  • Acute Coronary Syndrome / surgery
  • Aged
  • Alleles
  • Asian People / genetics
  • Aspirin / administration & dosage*
  • Blood Platelets / drug effects
  • China
  • Clopidogrel / administration & dosage*
  • Female
  • Glucuronosyltransferase / genetics
  • Humans
  • Logistic Models
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Percutaneous Coronary Intervention
  • Platelet Aggregation / drug effects
  • Platelet Aggregation Inhibitors / administration & dosage*
  • Polymorphism, Single Nucleotide*
  • Receptors, Cell Surface / genetics
  • Receptors, Purinergic P2Y12 / genetics
  • Thrombelastography

Substances

  • P2RY12 protein, human
  • PEAR1 protein, human
  • Platelet Aggregation Inhibitors
  • Receptors, Cell Surface
  • Receptors, Purinergic P2Y12
  • Clopidogrel
  • Glucuronosyltransferase
  • UGT2A1 protein, human
  • Aspirin