Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

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

Version 1 : Received: 25 December 2023 / Approved: 8 January 2024 / Online: 8 January 2024 (02:22:48 CET)
Version 2 : Received: 28 August 2024 / Approved: 29 August 2024 / Online: 30 August 2024 (05:14:56 CEST)

A peer-reviewed article of this Preprint also exists.

Monero-Paredes, M.; Santiago, E.; Carrasquillo-Carrion, K.; Renta, J.Y.; Rogozin, I.B.; Roche-Lima, A.; Duconge, J. Paraoxonase-1 as a Cardiovascular Biomarker in Caribbean Hispanic Patients Treated with Clopidogrel: Abundance and Functionality. Int. J. Mol. Sci. 2024, 25, 10657. Monero-Paredes, M.; Santiago, E.; Carrasquillo-Carrion, K.; Renta, J.Y.; Rogozin, I.B.; Roche-Lima, A.; Duconge, J. Paraoxonase-1 as a Cardiovascular Biomarker in Caribbean Hispanic Patients Treated with Clopidogrel: Abundance and Functionality. Int. J. Mol. Sci. 2024, 25, 10657.

Abstract

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 function (PRU), PON1 abundance by western blotting, and PON1 activity by enzymatic assays were measured. PON1 genotyping and computational haplotype phasing were performed for two genetic loci (rs662 and rs854560). No statistical differences in mean relative PON1 abundance were found among the groups (p> 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; p= 0.004). PON1 activity among carriers of the most prevalent PON1 haplotype (AA|AA) was significantly lower than in wild-types (7.90 µU/mL vs 22.03 µU/mL; p= 0.005). Our findings suggested that PON1 is a potential biomarker of cardiovascular disease severity in Caribbean Hispanics.

Keywords

PON1; Clopidogrel; Caribbean Hispanics; Cardiovascular Diseases; Resistance

Subject

Medicine and Pharmacology, Cardiac and Cardiovascular Systems

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