Analysis of the CYP2C19 genotype associated with bleeding in Serbian
STEMI patients who have undergone primary PCI
and treatment with clopidogrel
Received: 19 September 2017 /Accepted: 8 December 2017 /Published online: 19 December 2017
Springer-Verlag GmbH Germany, part of Springer Nature 2017, corrected publication February/2018
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) vari-
ants were analysed in all 108 patients. Additionally, sequencing of all nine exons, 5′UTR and 3′UTR in the rs11568732 carriers
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.
Clopidogrel, along with aspirin, is a cornerstone of therapy
used to reduce the risk of recurrent ischaemic events or death
in patients with acute coronary syndromes, which includes
patients with ST segment elevation myocardial infarction
(STEMI) undergoing primary percutaneous coronary inter-
vention (PCI). Because of that, clopidogrel has a great medical
significance. Despite launching a new generation of antiplate-
let drugs which can substitute clopidogrel, it is still widely
used [1, 2].
The correct Author names are shown in this paper.
The original version of this article was revised.
Electronic supplementary material The online version of this article
(https://doi.org/10.1007/s00228-017-2401-5) contains supplementary
material, which is available to authorized users.
* Ljiljana Rakicevic
Institute of Molecular Genetics and Genetic Engineering, University
of Belgrade, Vojvode Stepe 444a, P.O. Box 23,
11010 Belgrade, Serbia
Emergency Department, Clinic for Cardiology, Clinical Center of
Serbia, Belgrade, Serbia
Faculty of Medicine, University of Belgrade, Belgrade, Serbia
European Journal of Clinical Pharmacology (2018) 74:443–451