Effect of CYP2C19 genetic variants on bleeding and major adverse cardiovascular events in a cohort of Arab patients undergoing percutaneous coronary intervention and stent implantation
Author | Ali, Zainab Omer |
Author | Bader, Loulia |
Author | Mohammed, Shaaban |
Author | Arafa, Salaheddin |
Author | Arabi, Abdulrahman |
Author | Cavallari, Larisa |
Author | Langaee, Taimour |
Author | Mraiche, Fatima |
Author | Rizk, Nasser |
Author | Awaisu, Ahmed |
Author | Shahin, Mohamed H. |
Author | Elewa, Hazem |
Available date | 2022-12-15T07:16:22Z |
Publication Date | 2022 |
Publication Name | Pharmacogenetics and Genomics |
Resource | Scopus |
Abstract | Introduction One-third of patients have clopidogrel resistance that may lead to major adverse cardiac events (MACEs). By contrast, it was found that some clopidogrel-treated patients have hyperresponsive platelets that are associated with higher bleeding risk. Several studies have shown that polymorphisms in the gene encoding the CYP2C19 contribute to the variability in response to clopidogrel. Data on genetic and nongenetic factors affecting clopidogrel response in the Arab population are scarce. In this prospective cohort study, we sought to assess the association between the increased function allele (CYP2C19?17) and bleeding events, and validate the effect of the CYP2C19 genetic variants and nongenetic factors on the incidence of MACEs. Methods Blood samples were collected from patients that were undergoing percutaneous coronary intervention and receiving clopidogrel at the Heart Hospital, a specialist tertiary hospital in Doha, Qatar. Patients were followed for 12 months. Genotyping was performed for CYP2C19?2, ?3, and ?17 using TaqMan assays. Results In 254 patients, the minor allele frequencies were 0.13, 0.004, and 0.21 for ?2, ?3, and ?17, respectively. Over a 12-month follow-up period, there were 21 bleeding events (8.5 events/100 patient-year). CYP2C19?17 carriers were found to be associated with increased risk of bleeding (OR, 21.6; 95% CI, 4.8-96.8; P < 0.0001). CYP2C19?2 or ?3 carriers were found to be associated with increased risk of baseline and incident MACE combined (OR, 8.4; 95% CI, 3.2-23.9; P < 0.0001). Conclusion This study showed a significant association between CYP2C19?17 allele and the increased risk of bleeding, and CYP2C19?2 or ?3 with MACE outcomes. 2022 Lippincott Williams and Wilkins. All rights reserved. |
Sponsor | The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This research was funded by Hamad Medical Corporation, Doha, Qatar (grant number: IRGC-02-NI-052). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. |
Language | en |
Publisher | Lippincott Williams and Wilkins |
Subject | antiplatelets bleeding clopidogrel CYP2C19 pharmacogenomics thrombosis |
Type | Article |
Pagination | 183-191 |
Issue Number | 5 |
Volume Number | 32 |
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