Abstract
Clopidogrel, an oral platelet P2Y12 receptor blocker, is used in the treatment of acute coronary syndrome. Interindividual variability in treatment response and the occurrence of adverse effects has been attributed to genetic variants in CYP2C19. The analysis of relevant pharmacogenes in ethnically heterogeneous and poorly studied populations contributes to the implementation of personalized medicine. We analyzed the coding and regulatory regions of CYP2C19 in 166 patients with acute coronary syndrome (ACS) treated with clopidogrel. The allele frequencies of CYP2C19 alleles *1, *2, *4, *17, *27 and *33 alleles were 86.1%, 7.2%, 0.3%, 10.2%, 0.3% and 0.3%, respectively. A new potentially pathogenic mutation (p.L15H) and five intronic variants with potential splicing effects were detected. In 14.4% of the patients, a new haplotype in strong linkage disequilibrium was identified. The clinical outcome indicated that 13.5% of the patients presented adverse drugs reactions with a predominance of bleeding while 25% of these patients were carriers of at least one polymorphic allele. We propose that new regulatory single-nucleotide variants (SNVs) might potentially influence the response to clopidogrel in Colombian individuals.
Highlights
In order to assess the potential association of CYP2C19 polymorphic alleles with platelet reactivity in acute coronary syndrome (ACS) patients, we studied the promoter, coding regions and intron-exon boundaries of the gene
Most cases were over 50 years old, and the predominant type of coronary syndrome was acute myocardial infarction with ST elevation (63.2%). 32.5% of patients previously presented one or more ACS when recruited into the study and nearly 30% presented a comorbidity (Table 1)
CYP2C19 was sequenced in the 166 ACS patients, and we identified a total of 41 single nucleotide variations (SNVs)
Summary
Dual antiplatelet therapy with clopidogrel and aspirin has been routinely recommended in the American College of Cardiology/American Heart Association guidelines for patients with acute coronary syndrome to prevent atherothrombotic events [1,2]. Clopidogrel is an inactive prodrug that is converted into an active metabolite by two-step biotransformation. This metabolite binds irreversibly to the purinergic adenosine diphosphate (ADP) platelet receptor P2Y12 and inhibits ADP-stimulated platelet aggregation [3,4]. Clopidogrel is one of the most widely used platelet antiaggregant with over 40,000,000 patients prescribed worldwide [5,6]. Clopidogrel has high clinical efficacy, over 30%
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