The contribution of platelet glycoproteins (GPIa C807T and GPIba C-5T) and cyclooxygenase 2 (COX-2G-765C) polymorphisms to platelet response in patients treated with aspirin

Gene. 2013 Sep 10;526(2):118-21. doi: 10.1016/j.gene.2013.04.083. Epub 2013 May 18.

Abstract

Objective: Aspirin is an antiplatelet agent commonly used in treatment of patients with high risk to develop stroke and myocardial infarction. However, inter-individual variability regarding the inhibition of platelet function by aspirin is well documented. In this study, the correlation between platelet glycoproteins (GPIa C807T and GPIba C-5T) and cyclooxygenase 2 (COX-2G-765C) polymorphisms and antiplatelet response in patients treated with aspirin was investigated.

Methods: Jordanian adult patients (n=584) who are taking aspirin as an antiplatelet agent participated in the study. Platelet aggregation response was measured using Multiplate Analyzer® system. Polymerase chain reaction-restriction fragment length polymorphism assay (PCR-RFLP) was used for genotyping of the examined polymorphisms.

Results: Aspirin resistance was found in 15.8% of patients. Response to aspirin was significantly associated with GPIba C-5T polymorphism (P<0.05). However, the GPIa C807T and COX-2G-765C polymorphisms were not related to aspirin resistance (P>0.05).

Conclusion: A considerable fraction of the Jordanian population is resistant to the antiplatelet effect of aspirin, which might be related to GPIba C-5T polymorphism.

Keywords: Antiplatelet resistance; BMI; Body mass index; COX; COX 2; Cyclooxygenase 2; Cyclooxygenases; GPIIb/IIIa; GPIa; GPIbα; Glycosylated hemoglobin; HbA1(C); Jordan; MI; Myocardial infarction; NSIADs; Nonsteroidal antiinflammatory drugs; PCR–RFLP; Platelet glycoprotein IIb/IIIa; Platelet glycoprotein Ia; Platelet glycoprotein Ibα; Polymerase chain reaction restriction fragment length polymorphism; Polymorphism; Restriction fragment length polymorphism; SNPs; SPSS; Statistical Package for the Social Sciences; TIA; TXA2; Thromboxane A2; Transient ischemic attack; VWF; Von Willebrand factor; single nucleotide polymorphisms.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alleles
  • Aspirin / pharmacology*
  • Blood Platelets / drug effects*
  • Blood Platelets / metabolism*
  • Cyclooxygenase 2 / genetics*
  • Drug Resistance / genetics
  • Female
  • Gene Frequency
  • Genotype
  • Humans
  • Integrin alpha2 / genetics*
  • Jordan
  • Male
  • Membrane Glycoproteins / genetics*
  • Middle Aged
  • Platelet Aggregation / drug effects
  • Platelet Aggregation / genetics
  • Platelet Aggregation Inhibitors / pharmacology
  • Platelet Glycoprotein GPIb-IX Complex
  • Platelet Membrane Glycoproteins / genetics*
  • Polymorphism, Single Nucleotide*
  • Risk Factors

Substances

  • Integrin alpha2
  • Membrane Glycoproteins
  • Platelet Aggregation Inhibitors
  • Platelet Glycoprotein GPIb-IX Complex
  • Platelet Membrane Glycoproteins
  • adhesion receptor
  • Cyclooxygenase 2
  • Aspirin