Influência do haplótipo CYP2C:TG na resposta ao clopidogrel em pacientes cardiovasculares

Abstract

Clopidogrel is an essential antiplatelet prodrug in the prevention of thrombotic events in cardiovascular patients, especially after stent placement. However, variability in treatment response, partly attributed to CYP2C19 gene variants, challenges the drug's efficacy. The CYP2C:TG haplotype of the adjacent gene has been recently associated with increased CYP2C19 enzyme expression, but this claim remains controversial in the literature, and no studies have been conducted with Brazilian cardiovascular patients carrying this variant. This study aims to elucidate the impact of the CYP2C:TG haplotype on clopidogrel response in patients genotyped for the CYP2C19 *2, *3, and *17 alleles, using P2Y12 Reaction Units (PRU) from blood samples as the outcome measure. Genotyping was performed using real-time PCR with TaqMan™ assays, and point-of-care optical aggregometry was used to quantify platelet aggregation. To correlate the haplotype with PRU values, simple linear regression analysis was applied using the Python programming language and the statsmodels library. The results revealed the presence of the CYP2C:TG haplotype in 14.29% of the studied patients. PRU analysis in 56 genotyped patients indicated that the presence of the haplotype might be associated with lower PRU values, suggesting a potential influence on clopidogrel response, although the data did not show statistical significance. This study highlights the importance of considering additional genetic variants, such as the CYP2C:TG haplotype, to better understand the pharmacogenetics of clopidogrel and its implications in the treatment of cardiovascular patients.