Ítem
Acceso Abierto

The polygenic implication of clopidogrel responsiveness: Insights from platelet reactivity analysis and next-generation sequencing

Mostrar el registro sencillo de la publicación
dc.creatorEcheverría, Omarspa
dc.creatorAngulo-Aguado, Marianaspa
dc.creatorVela, Ricardospa
dc.creatorCalderón-Ospina, Carlosspa
dc.creatorParra, Katherinespa
dc.creatorContreras, Noraspa
dc.creatorMorel, Adrienspa
dc.creatorCabrera, Rodrigospa
dc.creatorRestrepo Fernández, Carlos Martínspa
dc.creatorRamírez Santana, Heily Carolinaspa
dc.creatorOrtega-Recalde, Oscar spa
dc.creatorRojas-Quintana, Manuel Eduardospa
dc.creatorMurcia, Luisaspa
dc.creatorGaviria-Sabogal, Cristian Camilospa
dc.creatorValero, Nattalyspa
dc.creatorFonseca Mendoza, Dora Janethspa
dc.date.accessioned2025-01-26T18:36:54Z
dc.date.available2025-01-26T18:36:54Z
dc.date.created2024-07-01spa
dc.date.issued2024-07-01spa
dc.descriptionClopidogrel is widely used worldwide as an antiplatelet therapy in patients with acute coronary disease. Genetic factors influence interindividual variability in response. Some studies have explored the polygenic contributions in the drug response, generating pharmacogenomic risk scores (PgxPRS). Importantly, these factors are less explored in underrepresented populations, such as Latin-American countries. Identifying patients at risk of high-on-treatment platelet reactivity (HTPR) is highly valuable in translational medicine. In this study we used a custom next-generation sequencing (NGS) panel composed of 91 single nucleotide polymorphisms (SNPs) and 28 genes related to clopidogrel metabolism, to analyze 70 patients with platelet reactivity values, assessed through closure time (CT). Our results demonstrated the association of SNPs with HTPR and non-HTPR, revealing the strongest associations with rs2286823 (OR: 5,0spa
dc.description95% CI: 1,02–24,48spa
dc.descriptionp: 0,03), rs2032582 (OR: 4,41spa
dc.description95% CI: 1,20–16,12spa
dc.descriptionp: 0,019), and rs1045642 (OR: 3,38spa
dc.description95% CI: 0,96–11,9spa
dc.descriptionp: 0,05). Bivariate regression analysis demonstrated the significant association of several SNPs with the CT value, a “surrogate” biomarker of clopidogrel response. Exploratory results from the LASSO regression model showed a high discriminatory capacity between HTPR and non-HTPR patients (AUC: 0,955), and the generated PgxPRS demonstrated a significant negative association between the risk score, CT value, and the condition of HTPR and non-HTPR. To our knowledge, our study addresses for the first time the analysis of the polygenic contribution in platelet reactivity using NGS and establishes PgxPRS derived from the LASSO model. Our results demonstrate the polygenic implication of clopidogrel response and offer insights applicable to the translational medicine of antiplatelet therapy in an understudied population.spa
dc.format.mimetypeapplication/pdfspa
dc.identifier.doihttps://doi.org/10.1371/journal.pone.0306445spa
dc.identifier.urihttps://repository.urosario.edu.co/handle/10336/44844
dc.language.isoengspa
dc.publisherPLOS ONEspa
dc.relation.ispartofPLOS ONEspa
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internationalspa
dc.rights.accesRightsinfo:eu-repo/semantics/openAccessspa
dc.rights.accesoAbierto (Texto Completo)spa
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/spa
dc.sourcePLOS ONEspa
dc.source.instnameinstname:Universidad del Rosariospa
dc.source.reponamereponame:Repositorio Institucional EdocURspa
dc.subjectClopidogrelspa
dc.subjectAntiplatelet therapyspa
dc.titleThe polygenic implication of clopidogrel responsiveness: Insights from platelet reactivity analysis and next-generation sequencingspa
dc.typearticlespa
dc.type.hasVersioninfo:eu-repo/semantics/publishedVersionspa
dc.type.spaArtículospa
Archivos
Bloque original
Mostrando1 - 1 de 1
Miniatura
Nombre:
The_polygenic_implication_of_clopidogrel_responsiveness.pdf
Tamaño:
1.86 MB
Formato:
Adobe Portable Document Format
Descripción:
Descargar
Colecciones
Artículos