Key result
Carriers of the CYP2C19 rs4244285 A-allele exhibited a significantly increased risk of major adverse cardiovascular events (OR 3.86) in clopidogrel-treated patients with acute coronary syndrome undergoing percutaneous coronary intervention.
Why the study?
The study evaluated the impact of clopidogrel-related gene polymorphisms on recurrent thrombotic events and cardiovascular death in ACS patients following PCI.
Do specific clopidogrel-related gene polymorphisms predict the risk of MACE in ACS patients undergoing PCI and receiving clopidogrel-based dual antiplatelet therapy?
Case-Control (n=200)
No
Do specific clopidogrel-related gene polymorphisms predict the risk of MACE in ACS patients undergoing PCI and receiving clopidogrel-based dual antiplatelet therapy?
Answers are grounded in this paper and cite their sources.
Specific genetic polymorphisms in PEAR1, PON1, CYP2C19, and CYP1A2 significantly increase the risk of MACE in ACS patients treated with clopidogrel after PCI, highlighting the potential utility of genetic testing for personalized antiplatelet therapy.
Objective: The objective of this study was to evaluate the impact of clopidogrel-related gene polymorphisms on the occurrence of recurrent thrombotic events and cardiovascular death in patients with acute coronary syndrome (ACS) following percutaneous coronary intervention (PCI). Methods: We conducted genotype testing for 26 specific loci mapped to 18 clopidogrel-associated genes in ACS patients who had undergone PCI and were receiving dual antiplatelet therapy only involving clopidogrel. We documented major adverse cardiovascular events (MACE) and clinical endpoints, analyzing the effect of genetic polymorphisms on treatment outcomes. Results: A total of 200 patients were enrolled in the study, with ischemic events occurring in 21 cases. Carriers of the T-allele for rs41273215 ( PEAR1 ), rs662 ( PON1 ), and the A-allele for rs4244285 ( CYP2C19 ), as well as the C-allele for rs762551 ( CYP1A2 ), exhibited a significant increase in the risk of MACE (OR = 2.76, 95% CI = 1.46– 5.22, P = 0.002; OR = 3.72, 95% CI = 1.82– 7.64, P = 0.0003; OR = 3.86, 95% CI = 1.89– 7.86, P = 0.0002; OR = 2.40, 95% CI = 1.27– 4.55, P = 0.007). Notably, the variant T-allele of rs168753 ( F2R ) was associated with a significant reduction in the risk of such events (OR = 0.29, 95% CI = 0.12– 0.67, P = 0.004). No significant associations were found between other single nucleotide polymorphisms (SNPs) and clinical endpoints. Conclusion: Polymorphisms in rs41273215 ( PEAR1 ), rs662 ( PON1 ), rs4244285 ( CYP2C19 ), and rs762551 ( CYP1A2 ) were correlated with an increased risk of MACE in PCI patients. Conversely, the rs168753 ( F2R ) polymorphism was linked to improved cardiovascular outcomes. Genotyping for these polymorphisms could be instrumental in identifying patients at heightened risk for MACE.
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Du et al. (2024) conducted a case-control in Acute Coronary Syndrome (ACS) (n=200). CYP2C19 rs4244285 A-allele vs. Non-carriers was evaluated on Major adverse cardiovascular events (MACE) (OR 3.86, 95% CI 1.89-7.86, p=0.0002). Carriers of the CYP2C19 rs4244285 A-allele exhibited a significantly increased risk of major adverse cardiovascular events (OR 3.86) in clopidogrel-treated patients with acute coronary syndrome undergoing percutaneous coronary intervention.
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