Evidence map›Paper›PMID 41165802›Full record

ArticleInflammation research : official journal of the European Histamine Research Society ... [et al.]2025

Beyond CYP2C19: inflammation and angiogenesis gene variants drive clopidogrel resistance in CAD patients.

Foddha Hajer, Aouadi Malek, Abderrahmane Amani, Omrani Rahma, Ben Hamda Khaldoun, Foddha Abdelhak, Omezzine Asma, Haj Khelil Amel, Chouchene Saoussen

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Article in Inflammation research : official journal of the European Histamine Research Society ... [et al.], 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Recent research progress on the mechanisms of clopidogrel resistance.European journal of clinical pharmacology · 2026
    Review
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

9 authors.

Foddha HajerLaboratory of Human Genome and Multifactorial Diseases (LR12ES07), Faculty of Pharmacy, University of Monastir, BP N 74, Street Tahar Haddad, 5000, Monastir, Tunisia. hajer.foddha@hotmail.fr.ORCID https://orcid.org/0000-0003-1490-3772
Aouadi MalekDepartment of Hematology, FattoumaBourguiba Hospital, University of Monastir, Monastir, Tunisia.
Abderrahmane AmaniBiochemistry Department, LR12SP11, Sahloul University Hospital, University of Sousse, Sousse, Tunisia.
Omrani RahmaLaboratory of Analysis, Treatment and Valorization of Environmental Pollutants and Products, Faculty of Pharmacy, Monastir University, Monastir, Tunisia.
Ben Hamda KhaldounCardiology Department, FattoumaBourguiba Hospital, University of Monastir, Monastir, Tunisia.
Foddha AbdelhakCardiology Department, FattoumaBourguiba Hospital, University of Monastir, Monastir, Tunisia.
Omezzine AsmaBiochemistry Department, LR12SP11, Sahloul University Hospital, University of Sousse, Sousse, Tunisia.
Haj Khelil AmelLaboratory of Human Genome and Multifactorial Diseases (LR12ES07), Faculty of Pharmacy, University of Monastir, BP N 74, Street Tahar Haddad, 5000, Monastir, Tunisia.
Chouchene SaoussenLaboratory of Human Genome and Multifactorial Diseases (LR12ES07), Faculty of Pharmacy, University of Monastir, BP N 74, Street Tahar Haddad, 5000, Monastir, Tunisia.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundClopidogrel resistance remains a significant clinical challenge in coronary artery disease (CAD), with traditional explanations focusing on CYP450 polymorphisms. However, emerging evidence highlights the critical role of inflammation and angiogenesis in modulating platelet reactivity and clopidogrel responsiveness. Genetic variants in these pathways may represent under recognized determinants of treatment failure. This pilot study investigated the association between single nucleotide polymorphisms (SNPs) in inflammation- (CCR2, CCL5, CCL2) and angiogenesis-related (KDR, VEGFA) genes and clopidogrel resistance.

methodsIn a cross-sectional study of 135 Tunisian CAD patients on dual antiplatelet therapy, clopidogrel response was assessed using VerifyNow P2Y12 assay (resistance defined as PRU  ≥  208). Nine SNPs were genotyped via PCR-RFLP. Associations were evaluated using logistic regression, adjusting for covariates.

resultsThe CCL5 rs2280789-C allele conferred a 3.4-fold increased resistance risk (OR = 3.40 (1.54-7.48), p =  0.002), while the CCR2 rs1799864-A allele was protective (OR =  0.30 (0.10-0.84), p =  0.02). The KDR rs1870377-AA genotype tripled resistance odds (OR =  3.05 (1.05-8.83), p =  0.04). A polygenic model revealed synergistic effects: 53% of non-responders carried  ≥ 2 risk genotypes (CCR2-GG, CCL5-TC, KDR-AA) vs. 15% of responders (OR = 6.51 (2.86-14.83), p < 0.001). No associations were found for VEGFA or CCL2 SNPs.

conclusionBeyond CYP450-mediated metabolism, clopidogrel resistance is driven by immuno-vascular mechanisms involving CCL5-mediated thrombo-inflammation, CCR2-dependent monocyte recruitment, and VEGFR2-linked endothelial dysfunction. These findings advocate for precision antiplatelet strategies integrating inflammatory and angiogenic pathways to optimize therapy.

Indexed as

ClopidogrelCoronary Artery DiseaseCytochrome P-450 CYP2C19Drug ResistancePlatelet Aggregation InhibitorsAgedAngiogenesisChemokine CCL2Chemokine CCL5Cross-Sectional StudiesFemaleHumansInflammationMaleMiddle AgedPolymorphism, Single NucleotideCCL2 protein, humanCCL5 protein, humanCCR2 protein, humanChemokine CCL2Chemokine CCL5ClopidogrelCYP2C19 protein, humanCytochrome P-450 CYP2C19KDR protein, humanPlatelet Aggregation InhibitorsReceptors, CCR2Vascular Endothelial Growth Factor AVascular Endothelial Growth Factor Receptor-2VEGFA protein, humanAngiogenesisCCL5CCR2Clopidogrel resistanceCoronary artery diseaseGenetic polymorphismInflammationKDRVEGFR

Identifiers

PMID41165802

What Socratic holds

Textmetadata
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.