Paraoxonase-1 as a Cardiovascular Biomarker in Caribbean Hispanic Patients Treated with Clopidogrel: Abundance and Functionality

• Published in: International journal of molecular sciences 2024-10, Vol.25 (19), p.10657
• Main Authors: Monero-Paredes, Mariangeli, Santiago, Ednalise, Carrasquillo-Carrion, Kelvin, Renta, Jessicca Y, Rogozin, Igor B, Roche-Lima, Abiel, Duconge, Jorge
• Format: Article
• Language: English
• Subjects: Acute coronary syndromes; Aged; Aryldialkylphosphatase - genetics; Aryldialkylphosphatase - metabolism; Atherosclerosis; Biomarkers; Biomarkers - blood; Blood platelets; Body mass index; Cardiovascular disease; Cardiovascular diseases; Cardiovascular Diseases - drug therapy; Cardiovascular Diseases - genetics; Caribbean Hispanics; Caribbean Region; Clopidogrel; Clopidogrel - therapeutic use; Coronary vessels; Development and progression; Dosage and administration; Drug therapy; Enzymes; Female; Genetic aspects; Genetic polymorphisms; Haplotypes; Health aspects; Heart attacks; Hispanic or Latino - genetics; Humans; Hypotheses; Latin Americans; Male; Middle Aged; Patients; Physiological aspects; Plasma; Platelet Aggregation Inhibitors - therapeutic use; Polymorphism; Polymorphism, Single Nucleotide; PON1; Proteins; resistance; Vein & artery diseases
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms251910657

Clopidogrel, a prescription drug to reduce ischemic events in cardiovascular patients, has been extensively studied in mostly European individuals but not among Caribbean Hispanics. This study evaluated the low abundance and reduced activity of paraoxonase-1 (PON1) in clopidogrel-resistant patients as a predictive risk biomarker of poor responders and disease severity in this population. Thirty-six patients on clopidogrel (cases divided into poor and normal responders) were enrolled, along with 11 cardiovascular patients with no clopidogrel indications (positive control) and 13 healthy volunteers (negative control). Residual on-treatment platelet reactivity unit (PRU), PON1 abundance by Western blotting, and PON1 activity by enzymatic assays were measured. genotyping and computational haplotype phasing were performed on 512 DNA specimens for two genetic loci (rs662 and rs854560). No statistical differences in mean relative PON1 abundance were found among the groups ( > 0.05). However, a significantly lower enzymatic activity was found in poor responders (10.57 ± 6.79 µU/mL) when compared to controls (22.66 ± 8.30 µU/mL and 22.21 ± 9.66 µU/mL; = 0.004). PON1 activity among carriers of the most prevalent haplotype (AA|AA) was significantly lower than in wild types (7.90 µU/mL vs. 22.03 µU/mL; = 0.005). Our findings suggested that PON1 is a potential biomarker of cardiovascular disease severity in Caribbean Hispanics.