Analysis of the CYP2C19 genotype associated with bleeding in Serbian STEMI patients who have undergone primary PCI and treatment with clopidogrel.

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  • Additional Information
    • Source:
      Publisher: Springer Country of Publication: Germany NLM ID: 1256165 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1432-1041 (Electronic) Linking ISSN: 00316970 NLM ISO Abbreviation: Eur J Clin Pharmacol Subsets: MEDLINE
    • Publication Information:
      Original Publication: Berlin, New York, Springer.
    • Subject Terms:
      Percutaneous Coronary Intervention*/adverse effects ; Pharmacogenomic Variants* ; Polymorphism, Single Nucleotide*; Cytochrome P-450 CYP2C19/*genetics ; Hemorrhage/*chemically induced ; Platelet Aggregation Inhibitors/*adverse effects ; ST Elevation Myocardial Infarction/*drug therapy ; Ticlopidine/*analogs & derivatives; Aged ; Chi-Square Distribution ; Clopidogrel ; Cytochrome P-450 CYP2C19/metabolism ; Female ; Genetic Predisposition to Disease ; Haplotypes ; Hemorrhage/enzymology ; Hemorrhage/genetics ; Humans ; Logistic Models ; Male ; Middle Aged ; Odds Ratio ; Pharmacogenetics ; Phenotype ; Platelet Aggregation Inhibitors/administration & dosage ; Retrospective Studies ; Risk Factors ; ST Elevation Myocardial Infarction/diagnosis ; Serbia ; Ticlopidine/administration & dosage ; Ticlopidine/adverse effects ; Treatment Outcome
    • Abstract:
      Purpose: Bleeding is one of the possible adverse events during clopidogrel therapy. The CYP2C19 gene is the most significant genetic factor which influences response to clopidogrel treatment. We aimed to examine the contribution of the CYP2C19 gene to bleeding occurrence during clopidogrel therapy in Serbian patients with ST segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI).
      Methods: This case-control study included 53 patients who experienced bleeding and 55 patients without bleeding. Bleeding events were defined and classified using the Bleeding Academic Research Consortium (BARC) criteria. All patients were prescribed daily doses of clopidogrel during the 1-year follow-up after PCI. The CYP2C19*17 (c.-806C>T, rs12248560), rs11568732 (c.-889T>G, CYP2C19*20), CYP2C19*2 (c.681G>A; rs4244285) and CYP2C19*3 (c.636G>A; rs4986893) variants were analysed in all 108 patients. Additionally, sequencing of all nine exons, 5'UTR and 3'UTR in the rs11568732 carriers was performed.
      Results: Association between bleeding (BARC type ≥ 2) and the CYP2C19*17 variant was not observed [odds ratio (OR), 0.53; 95% confidence interval (CI), 0.2-1.1; p = 0.107). The rs11568732 variant showed significant association with bleeding (OR, 3.7; 95% CI, 1.12-12.44; p = 0.025). Also, we found that the rs11568732 variant appears independently of haplotype CYP2C19*3B, which is contrary to the previous findings.
      Conclusions: Our results indicate the absence of CYP2C19*17 influence and turn the attention to the potential significance of the rs11568732 variant in terms of adverse effects of clopidogrel. However, it is necessary to conduct an independent conformation study in order to verify this finding. Also, an analysis of the functional implication of the rs11568732 variant is necessary in order to confirm the significance of this variant, both in relation to its influence on gene expression and in relation to its medical significance.
    • Comments:
      Erratum in: Eur J Clin Pharmacol. 2018 Feb 5;:. (PMID: 29404632)
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    • Contributed Indexing:
      Keywords: Bleeding; CYP2C19; Clopidogrel; PCI; Pharmacogenetics
    • Accession Number:
      0 (Platelet Aggregation Inhibitors)
      A74586SNO7 (Clopidogrel)
      EC 1.14.14.1 (CYP2C19 protein, human)
      EC 1.14.14.1 (Cytochrome P-450 CYP2C19)
      OM90ZUW7M1 (Ticlopidine)
    • Publication Date:
      Date Created: 20171221 Date Completed: 20180904 Latest Revision: 20181202
    • Publication Date:
      20240829
    • Accession Number:
      10.1007/s00228-017-2401-5
    • Accession Number:
      29260275