Targeted next-generation sequencing panel to investigate antiplatelet adverse reactions in acute coronary syndrome patients undergoing percutaneous coronary intervention with stenting

Antiplatelet therapy, the gold standard of care for patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI), is one of the therapeutic approaches most associated with the development of adverse drug reactions (ADRs). Although numerous studies have shown that p...

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Published in:Thrombosis research 2024-08, Vol.240, p.109060, Article 109060
Main Authors: Antúnez-Rodríguez, Alba, García-Rodríguez, Sonia, Pozo-Agundo, Ana, Sánchez-Ramos, Jesús Gabriel, Moreno-Escobar, Eduardo, Triviño-Juárez, José Matías, Martínez-González, Luis Javier, Dávila-Fajardo, Cristina Lucía
Format: Article
Language:English
Subjects:
Acute coronary syndrome
Adverse drug reactions
Cardiovascular drugs
Custom-targeted panel
Personalized medicine
Pharmacogenetics
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Summary:Antiplatelet therapy, the gold standard of care for patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI), is one of the therapeutic approaches most associated with the development of adverse drug reactions (ADRs). Although numerous studies have shown that pharmacological intervention based on a limited number of high-evidence variants (primarily CYP2C19*2 and *3) can reduce the incidence of major adverse cardiovascular events (MACEs), ADRs still occur at variable rates (10.1 % in our case) despite personalized therapy. This study aimed to identify novel genetic variants associated with the endpoint of MACEs 12 months after PCI by designing and analyzing a targeted gene panel. We sequenced 244 ACS-PCI-stent patients (109 with event and 135 without event) and 99 controls without structural cardiovascular disease and performed an association analysis to search for unexpected genetic variants. No single nucleotide polymorphisms reached genomic significance after correction, but three novel variants, including ABCA1 (rs2472434), KLB (rs17618244), and ZNF335 (rs3827066), may play a role in MACEs in ACS patients. These genetic variants are involved in regulating high-density lipoprotein levels and cholesterol deposition, and as they are regulatory variants, they may affect the expression of nearby lipid metabolism-related genes. Our findings suggest new targets (both at the gene and pathway levels) that may increase susceptibility to MACEs, but further research is needed to clarify the role and impact of the identified variants before these findings can be incorporated into the therapeutic decision-making process. Abbreviations: ABCA1, ATP binding cassette subfamily a member 1; ACS, acute coronary syndrome; Cv, cardiovascular; DNA, deoxyribonucleic acid; KLB, Klotho Beta; PGx, pharmacogenomics; ZNF335, zinc finger protein 335 [Display omitted] •Antiplatelets are drugs frequently implicated in the development of ADRs.•PGx helps select optimal drug and dose to improve ACS-ICP stent patients outcomes.•Certain ADRs cannot be prevented by preemptive genotyping of high-evidence variants.•We analyzed a custom gene panel for new variants for clinical consideration.•MACEs appear to be associated with intronic variants involved in lipid metabolism.
ISSN:0049-3848
1879-2472
1879-2472
DOI:10.1016/j.thromres.2024.109060