Is CYP2C Haplotype Relevant for Efficacy and Bleeding Risk in Clopidogrel-Treated Patients?

Scientific paper - Original scientific paper

• Author: Lana Ganoci
• Author: Jozefina Palić
• Author: Vladimir Trkulja
• Author: Katarina Starčević
• Author: Livija Šimičević
• Author: Nada Božina
• Author: Martina Lovrić-Benčić
• Author: Zdravka Poljaković
• Author: Tamara Božina
• Author's institution: University of Zagreb; School of Medicine; (Department of Internal Medicine)
• Author's institution: University of Zagreb; School of Medicine; (Department of Medical Chemistry, Biochemistry and Clinical Chemistry)
• Author's institution: University of Zagreb; School of Medicine; (Department of Neurology)
• Author's institution: University of Zagreb; School of Medicine; (Department of Pharmacology)
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Basic Medical Sciences; Pharmacology
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences; Neurology
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences; Internal Medicine

Abstract (english)

A recently discovered haplotype—CYP2C:TG—determines the ultrarapid metabolism of several CYP2C19 substrates. The platelet inhibitor clopidogrel requires CYP2C19-mediated activation: the risk of ischemic events is increased in patients with a poor (PM) or intermediate (IM) CYP2C19 metabolizer phenotype (vs. normal, NM; rapid, RM; or ultrarapid, UM). We investigated whether the CYP2C:TG haplotype affected efficacy/bleeding risk in clopidogrel-treated patients. Adults (n = 283) treated with clopidogrel over 3–6 months were classified by CYP2C19 phenotype based on the CYP2C19*2*17 genotype, and based on the CYP2C19/CYP2C cluster genotype, and regarding carriage of the CYP2:TG haplotype, and were balanced on a number of covariates across the levels of phenotypes/haplotype carriage. Overall, 45 (15.9%) patients experienced ischemic events, and 49 (17.3%) experienced bleedings. By either classification, the incidence of ischemic events was similarly numerically higher in PM/IM patients (21.6%, 21.8%, respectively) than in mutually similar NM, RM, and UM patients (13.2–14.8%), whereas the incidence of bleeding events was numerically lower (13.1% vs. 16.6–20.5%). The incidence of ischemic events was similar in CYP2C:TG carries and non-carries (14.1% vs. 16.1%), whereas the incidence of bleedings appeared mildly lower in the former (14.9% vs. 20.1%). We observed no signal to suggest a major effect of the CYP2C19/CYP2C cluster genotype or CYP2C:TG haplotype on the clinical efficacy/safety of clopidogrel.

• Keywords (english): Aged; Clopidogrel / adverse effects; Clopidogrel / therapeutic use; Cytochrome P-450 CYP2C19* / genetics; Female; Genotype; Haplotypes; Hemorrhage / chemically induced; Hemorrhage / genetics; Humans; Male; Middle Aged; Platelet Aggregation Inhibitors / adverse effects; Platelet Aggregation Inhibitors / therapeutic use; Ticlopidine / adverse effects; Ticlopidine / analogs & derivatives; Ticlopidine / therapeutic use
• Language: english
• Publication type: Scientific paper - Original scientific paper
• Publication status: Published
• Peer review: Peer review
• Publication version: Published version
• Journal title: Genes
• Numbering: vol. 15, no. 5, 607
• e-ISSN: 2073-4425
• DOI: https://doi.org/10.3390/genes15050607
• URN:NBN: urn:nbn:hr:105:179018
• Publication: 2024-05-10
• Project: Number: UIP-2020-02-8189; Title (croatian): Uloga farmakogenomike u predviđanju nuspojava kardiovaskularnih lijekova; Title (english): Pharmacogenomics in prediction of cardiovascular drugs adverse reaction; Acronym: PGx-CardioDrug; Leader: Tamara Božina; Jurisdiction: Croatia; Funding stream: Installation Research Projects
• Document URL: https://www.mdpi.com/2073-4425/15/5/607
• Type of resource: Text
• Access conditions: Open access
• Created on: 2025-02-05 14:15:28