Key result
CYP450 and ABCB1 polymorphisms are not linked to clopidogrel responsiveness in acute coronary syndrome.
Why the study?
Polymorphisms in genes encoding CYP enzymes and P-glycoprotein transporter could affect clopidogrel absorption and biotransformation, especially during the first critical hours after administration.
Do CYP450 and ABCB1 genetic polymorphisms affect platelet response to a 300 mg clopidogrel loading dose in Moroccan patients with acute coronary syndromes?
Observational (n=55)
No
Do CYP450 and ABCB1 genetic polymorphisms affect platelet response to a 300 mg clopidogrel loading dose in Moroccan patients with acute coronary syndromes?
Absolute Event Rate: 78.9% vs 52.8%
p-value: p=0.057
In a small cohort of Moroccan ACS patients, CYP450 polymorphisms did not significantly affect clopidogrel response, while the ABCB1 3435T variant showed a marginal trend toward clopidogrel non-responsiveness.
Does not support genotyping for clopidogrel response in Moroccan ACS; leaves open ABCB1 3435T role in larger multi-ethnic studies.
Introduction: Clopidogrel is an antiplatelet prodrug primarily prescribed to prevent or treat acute coronary syndrome (ACS) or acute ischemic stroke (IS), polymorphisms of genes encoding cytochrome P-450 (CYP) and P-glycoprotein transporter, could affect the efficiency of clopidogrel absorption and biotransformation, especially during the first critical hours following its administration. Methods: The present study was designed to investigate the potential association of clopidogrel responsiveness and 14 polymorphisms in the genes encoding the CYPs (CYP2C9, 2C19, 3A4, 3A5, 1A2, and 2B6), the ATP binding cassette subfamily B member 1 (ABCB1). Platelet aggregation activity was measured after 8h of 300mg clopidogrel administration for fifty-five ACS patients. Results: There was no significant association between polymorphism of the studied CYPs and clopidogrel responsiveness (P>0.05). The frequency of the ABCB1 3435 T allele in clopidogrel non-responders was higher (78.9%) compared to responders (52.8%), but this difference was not significant (P=0.057). Demographic characteristics, comorbidities, concomitant treatments were not associated with clopidogrel response. Discussion: There was no effect of the studied genetic variations and demographic factors on the platelet activity of clopidogrel in Moroccan ACS patients.
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Mouhrach et al. (2023) conducted an observational in Acute Coronary Syndromes (n=55). CYP450 and ABCB1 genetic polymorphisms (specifically ABCB1 3435 T allele) vs. Wild-type genotypes / Responders was evaluated on Frequency of the ABCB1 3435 T allele in clopidogrel non-responders versus responders (PRU > 208 at 8 hours) (p=0.057). CYP450 and ABCB1 genetic polymorphisms were not significantly associated with clopidogrel responsiveness in Moroccan patients with acute coronary syndromes, though the ABCB1 3435 T allele showed a marginal trend toward non-response (78.9% vs 52.8%, p=0.057).
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