Evidence map›Paper›PMID 38991024›Full record

ArticlePloS one2024

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

Omar Echeverría, Mariana Angulo-Aguado, Ricardo Vela, Carlos Calderón-Ospina, Katherine Parra, Nora Contreras, Adrien Morel, Rodrigo Cabrera, Carlos Restrepo, Carolina Ramírez-Santana and 6 more

Abstract read
In one paragraph

Article in PloS one, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Review
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors.

Omar EcheverríaSchool of Medicine and Health Sciences, Center for Research in Genetics and Genomics (CIGGUR), Institute of Translational Medicine (IMT), Universidad Del Rosario, Bogotá D.C., Colombia.ORCID https://orcid.org/0009-0000-6753-0178
Mariana Angulo-AguadoSchool of Medicine and Health Sciences, Center for Research in Genetics and Genomics (CIGGUR), Institute of Translational Medicine (IMT), Universidad Del Rosario, Bogotá D.C., Colombia.
Ricardo VelaSchool of Medicine and Health Sciences, Center for Research in Genetics and Genomics (CIGGUR), Institute of Translational Medicine (IMT), Universidad Del Rosario, Bogotá D.C., Colombia.
Carlos Calderón-OspinaSchool of Medicine and Health Sciences, Center for Research in Genetics and Genomics (CIGGUR), Institute of Translational Medicine (IMT), Universidad Del Rosario, Bogotá D.C., Colombia.
Katherine ParraHospital Universitario Mayor-Méderi-Universidad del Rosario, Bogotá D.C., Colombia.
Nora ContrerasSchool of Medicine and Health Sciences, Center for Research in Genetics and Genomics (CIGGUR), Institute of Translational Medicine (IMT), Universidad Del Rosario, Bogotá D.C., Colombia.
Adrien MorelSchool of Medicine and Health Sciences, Center for Research in Genetics and Genomics (CIGGUR), Institute of Translational Medicine (IMT), Universidad Del Rosario, Bogotá D.C., Colombia.
Rodrigo CabreraSchool of Medicine and Health Sciences, Center for Research in Genetics and Genomics (CIGGUR), Institute of Translational Medicine (IMT), Universidad Del Rosario, Bogotá D.C., Colombia.
Carlos RestrepoSchool of Medicine and Health Sciences, Center for Research in Genetics and Genomics (CIGGUR), Institute of Translational Medicine (IMT), Universidad Del Rosario, Bogotá D.C., Colombia.ORCID https://orcid.org/0000-0001-6410-0084
Carolina Ramírez-SantanaCenter for Autoimmune Diseases Research (CREA), School of Medicine and Health Sciences, Universidad del Rosario, Bogotá D.C., Colombia.
Oscar Ortega-RecaldeSchool of Medicine and Health Sciences, Center for Research in Genetics and Genomics (CIGGUR), Institute of Translational Medicine (IMT), Universidad Del Rosario, Bogotá D.C., Colombia.
Manuel Eduardo Rojas-QuintanaCenter for Autoimmune Diseases Research (CREA), School of Medicine and Health Sciences, Universidad del Rosario, Bogotá D.C., Colombia.ORCID https://orcid.org/0000-0002-8604-4658
Luisa MurciaHospital Universitario Mayor-Méderi-Universidad del Rosario, Bogotá D.C., Colombia.ORCID https://orcid.org/0000-0003-2998-8561
Cristian Camilo Gaviria-SabogalSchool of Medicine and Health Sciences, Center for Research in Genetics and Genomics (CIGGUR), Institute of Translational Medicine (IMT), Universidad Del Rosario, Bogotá D.C., Colombia.ORCID https://orcid.org/0009-0004-9482-4373
Nattaly ValeroSchool of Medicine and Health Sciences, Center for Research in Genetics and Genomics (CIGGUR), Institute of Translational Medicine (IMT), Universidad Del Rosario, Bogotá D.C., Colombia.
Dora Janeth Fonseca-MendozaSchool of Medicine and Health Sciences, Center for Research in Genetics and Genomics (CIGGUR), Institute of Translational Medicine (IMT), Universidad Del Rosario, Bogotá D.C., Colombia.ORCID https://orcid.org/0000-0002-7323-6570

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

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 (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: 5,0; 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 "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.

Indexed as

Blood PlateletsClopidogrelHigh-Throughput Nucleotide SequencingPlatelet Aggregation InhibitorsPolymorphism, Single NucleotideAgedFemaleHumansMaleMiddle AgedMultifactorial InheritanceTiclopidineClopidogrelPlatelet Aggregation InhibitorsTiclopidine

Identifiers

PMID38991024
PMCPMC11239111

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.