Análisis farmacogenómico mediante secuenciación de siguiente generación (NGS) para la estimación de la implicación poligénica en la reactividad plaquetaria en pacientes tratados con clopidogrel

Translated title of the contribution: Pharmacogenomic analysis by next generation sequencing (NGS) for estimation of polygenic involvement in platelet reactivity in patients treated with clopidogrel

Omar Echeverría-Gómez, Mariana Angulo-Aguado, Carlos Alberto Calderon Ospina, Katherine Parra-Abaunza, Nora Constanza Contreras Bravo, Adrien Morel, Rodrigo Cabrera Perez, Carlos Martin Restrepo Fernandez, Heily Carolina Ramirez Santana, Oscar Javier Ortega Recalde, Manuel Eduardo Rojas Quintana, Luisa Murcia-Soriano, Cristian Gaviria-Sabogal, Dora Janeth Fonseca Mendoza

Research output: Contribution to conferencePosterpeer-review

Abstract

Clopidogrel 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 (HPTR) 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: 5.0; 95% CI: 1.02-24.48; p: 0.03), rs2032582 (OR: 4.41; 95% CI: 1.20-16.12; p: 0.019), and rs1045642 (OR: 3.38; 95% CI: 0.96-11.9; p: 0.05). Bivariate regression analysis demonstrated the significant association of several SNPs with the CT value, a biomarker of clopidogrel response. Exploratory results from the LASSO regression model showed a high discriminatory capacity between HPTR and non-HPTR patients (AUC: 0.955), and the generated PgxPRS demonstrated a significant negative association between the risk score, CT value, and the condition of HPTR and non-HPTR. 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.
Translated title of the contributionPharmacogenomic analysis by next generation sequencing (NGS) for estimation of polygenic involvement in platelet reactivity in patients treated with clopidogrel
Original languageSpanish (Colombia)
Pages1-1
Number of pages1
StateSubmitted - Apr 12 2024
EventVIII Encuentro de Investigaciones CIMED - Double Tree by Hilton, Bogotá, Colombia
Duration: Apr 11 2024Apr 12 2024

Conference

ConferenceVIII Encuentro de Investigaciones CIMED
Country/TerritoryColombia
CityBogotá
Period4/11/244/12/24

All Science Journal Classification (ASJC) codes

  • Genetics

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