Related Experiment Videos
Increased clopidogrel response is associated with ABCC3 expression: a pilot study
André Ducati Luchessi1, Vivian Nogueira Silbiger, Alvaro Cerda
1Faculty of Pharmaceutical Science, Department of Clinical and Toxicological Analyses, University of Sao Paulo, Sao Paulo, Brazil. adluchessi@usp.br
Insights
Low ABCC3 gene expression in peripheral blood cells is linked to a better response to clopidogrel treatment in coronary artery disease patients. Further research is needed to understand this clopidogrel-ABCC3 relationship.
Area of Science:
- Pharmacogenomics
- Cardiovascular Medicine
- Molecular Biology
Background:
- Coronary artery disease (CAD) patients often receive clopidogrel, but responses vary.
- Gene expression, specifically ABCB1 and ABCC3, may influence clopidogrel efficacy.
- Investigating these genetic markers can optimize antiplatelet therapy.
Purpose of the Study:
- To examine the association between ABCB1 and ABCC3 gene expression in peripheral blood cells (PBC) and clopidogrel response in CAD patients.
- To determine if genetic variations predict treatment outcomes.
Main Methods:
- Twenty-six male CAD patients (50-70 years) on clopidogrel therapy were studied.
- Platelet reactivity was measured using P2Y12 Reaction Units (PRU).
- ABCB1 and ABCC3 mRNA expression levels in PBC were quantified via qPCR.
Main Results:
- A significant association was found between ABCC3 expression and clopidogrel response.
- Higher ABCC3 expression correlated with reduced clopidogrel efficacy (1.7 times more expressed in non-responders).
- Low ABCC3 mRNA expression (Qe1) significantly increased the likelihood of a good clopidogrel response (OR: 18.00, p=0.001).
Conclusions:
- Reduced ABCC3 mRNA expression in PBC is a potential biomarker for enhanced clopidogrel response in CAD.
- The functional role of ABCC3 in clopidogrel metabolism and action requires further investigation.
Background:
The aim of this study was investigate the relationship between ABCB1 and ABCC3 gene expressions in peripheral blood cells (PBC) and the response to clopidogrel in patients with coronary arterial disease (CAD).
Methods:
Twenty-six male CAD patients (50-70 years) under treatment with clopidogrel (75 mg/day) for at least 5 days were selected. Blood samples were obtained to evaluate platelet reactivity and ABCB1 and ABCC3 mRNA expression. Platelet reactivity was measured in P2Y12 Reaction Units (PRU) using VerifyNow. RNA was extracted from PBC and mRNA levels were measured by qPCR, using GAPD as a reference gene.
Results:
Platelet response to clopidogrel was categorized in to PRU quartiles. Individuals with PRU values within the first quartile (Q1, <151 units) were considered good responders, while those who had PRU within the fourth quartile (Q4, PRU>260) were considered non-responders. ABCC3 was 1.7 times more expressed in Q4 than in Q1 PRU group (p=0.048). Moreover, CAD patients with low ABCC3 expression (Qe1, <2.5×10(-3)) had higher probability to have a good response to clopidogrel (OR: 18.00, 95%CI: 1.90-169.99, p=0.001). Univariate linear regression analysis demonstrated that low ABCC3 mRNA expression contributed with a reduction of 73 PRU in relation to the patients with expression value higher than 2.5×10(-3) (p=0.027). Neither ABCB1 mRNA levels nor clinical variables studied influenced PRU values.
Conclusions:
Low ABCC3 mRNA expression in peripheral blood cells is associated with increased clopidogrel response, but further studies are needed to describe the functional relationship of clopidogrel with the ABCC3.
Related Concept Videos
Pharmacogenomics: Identification of New Drug Targets
Pharmacogenetics of Drug Transporters: P-Glycoprotein and Solute Carrier Transporters
Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu
Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase
Acute Coronary Syndrome III: Diagnostic Studies
Antiplatelet Drugs: Prostaglandin Synthesis, P2Y12 and Glycoprotein IIb/IIIa Inhibitors
Prostaglandin synthesis inhibitors, exemplified by the widely known aspirin, wield their power by irreversibly acetylating...