Association of CYP2C19, CYP3A5 and GPIIb/IIIa gene polymorphisms with Aspirin and Clopidogrel Resistance in a cohort of Indian patients with Coronary Artery Disease.

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  • Additional Information
    • Source:
      Publisher: Blackwell Scientific Publications Country of Publication: England NLM ID: 101300213 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1751-553X (Electronic) Linking ISSN: 17515521 NLM ISO Abbreviation: Int J Lab Hematol Subsets: MEDLINE
    • Publication Information:
      Original Publication: Oxford : Blackwell Scientific Publications, c2007-
    • Subject Terms:
      Polymorphism, Genetic*; Aspirin/*therapeutic use ; Coronary Artery Disease/*drug therapy ; Coronary Artery Disease/*genetics ; Cytochrome P-450 CYP2C19/*genetics ; Cytochrome P-450 CYP3A/*genetics ; Drug Resistance/*genetics ; Platelet Glycoprotein GPIIb-IIIa Complex/*genetics ; Ticlopidine/*analogs & derivatives; Aged ; Alleles ; Antigens, Human Platelet/genetics ; Aspirin/administration & dosage ; Case-Control Studies ; Clopidogrel ; Cohort Studies ; Comorbidity ; Coronary Artery Disease/diagnosis ; Female ; Genotype ; Humans ; India ; Integrin beta3 ; Male ; Middle Aged ; Platelet Aggregation Inhibitors/administration & dosage ; Platelet Aggregation Inhibitors/therapeutic use ; Polymorphism, Single Nucleotide ; Risk Factors ; Ticlopidine/administration & dosage ; Ticlopidine/therapeutic use ; Treatment Outcome
    • Abstract:
      Introduction: Dual antiplatelet therapy with clopidogrel and aspirin is the current standard of care in the management of patients with coronary artery disease (CAD) and acute coronary syndrome (ACS). The variability in response to these antiplatelet agents may be due to the underlying genetic diversity. This study was designed to determine the resistance to aspirin and clopidogrel in Indian patients and to look for correlation, if any, with selected polymorphisms.
      Methods: Platelet function testing by light transmission aggregometry was performed on 72 patients with CAD/ACS who were stable on dual antiplatelet therapy (clopidogrel 75 mg OD and aspirin 150 mg OD) along with 72 controls. Aspirin resistance was considered as mean platelet aggregation ≥ 70% with 10 μm ADP and ≥ 20% with 0.75 mm arachidonic acid. Clopidogrel resistance was defined as <10% decrease from the baseline in platelet aggregation in response to ADP 10 μm and semi-response as <30% decrease from the baseline. Polymorphisms CYP2C19*2, *3, CYP3A5*3 and PLA1/A2 were genotyped.
      Results: We found 51.4% patients with inadequate response to clopidogrel (1.4% resistant and 50% semi-responders) and 5.5% patients semi-responders to aspirin, none being completely resistant. The genotype and allele frequencies of CYP2C19*2 and PLA1/A2 gene polymorphisms were significantly different between clopidogrel semi-responders and responders. Carriers of CYP2C19*2 and CYP3A5*3 showed diminished inhibition of platelet aggregation. No significant correlation was found between coronary events, type of coronary intervention with clopidogrel nonresponsiveness.
      Conclusion: Unlike aspirin, a high proportion of partial responders to clopidogrel were identified. In an interim analysis on 72 Indian patients, a significant association was found between CYP2C19*2 and PLA1/A2 in clopidogrel semi-responders.
      (© 2015 John Wiley & Sons Ltd.)
    • Contributed Indexing:
      Keywords: Drug Resistance; aspirin; clopidogrel; gene; molecular genetics; platelets; polymorphisms
    • Accession Number:
      0 (Antigens, Human Platelet)
      0 (ITGB3 protein, human)
      0 (Integrin beta3)
      0 (Platelet Aggregation Inhibitors)
      0 (Platelet Glycoprotein GPIIb-IIIa Complex)
      0 (human platelet antigen 1b)
      A74586SNO7 (Clopidogrel)
      EC 1.14.14.1 (Cytochrome P-450 CYP2C19)
      EC 1.14.14.1 (Cytochrome P-450 CYP3A)
      OM90ZUW7M1 (Ticlopidine)
      R16CO5Y76E (Aspirin)
    • Publication Date:
      Date Created: 20150813 Date Completed: 20161013 Latest Revision: 20220408
    • Publication Date:
      20240829
    • Accession Number:
      10.1111/ijlh.12416
    • Accession Number:
      26264906