Key result
Targeted sequencing of 343 individuals identified three novel variants (in ABCA1, KLB, ZNF335) potentially associated with MACEs at 12 months, though none reached genomic significance.
Why the study?
Adverse drug reactions still occur at variable rates despite personalized antiplatelet therapy based on known genetic variants in ACS patients undergoing PCI.
Do novel genetic variants identified by targeted next-generation sequencing associate with MACEs at 12 months in ACS patients undergoing PCI?
Case-Control (n=343)
Do novel genetic variants identified by targeted next-generation sequencing associate with MACEs at 12 months in ACS patients undergoing PCI?
Answers are grounded in this paper and cite their sources.
Targeted sequencing identified three novel genetic variants potentially associated with MACEs in ACS patients undergoing PCI, though none reached genomic significance after correction.
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.
No takes yet. Share an insight, caveat, or question.
Antúnez-Rodríguez et al. (2024) conducted a case-control in Acute coronary syndrome undergoing percutaneous coronary intervention with stenting (n=343). Genetic variants (ABCA1, KLB, ZNF335) vs. Absence of variants / controls was evaluated on Major adverse cardiovascular events (MACEs) 12 months after PCI. Targeted sequencing of 343 individuals identified three novel variants (in ABCA1, KLB, ZNF335) potentially associated with MACEs at 12 months, though none reached genomic significance.
Synapse has enriched 10 related papers. Consider them for comparative context: