Paraoxonase-1 Deficiency does not Influence Clopidogrel Antiplatelet Function in Mice

Abstract

Background: Clopidogrel is an antiplatelet agent used in the treatment of vascular diseases. It requires in vivo bio activation linked to the cytochrome P450. Several studies reported that paraoxonase-1 (PON1) was a crucial enzyme in clopidogrel activation, and that patients carrying a variant of the PON1192 gene polymorphism have a high risk of thrombosis. However, these reports were not confirmed by subsequent results. The present study was aimed at investigating whether PON1 deficiency affects the biological action of clopidogrel in mice.

Association between Paraoxonase-1 p.Q192R Polymorphism and Coronary Artery Disease susceptibility in the Colombian Population

“…A recent study using PON1-deficient mice, in which platelet reactivity was assessed by PFA-100, showed PON1 deficiency does not influence the antiplatelet action of clopidogrel in mice. 54 These results reinforce the hypothesis that the enzyme is not involved in clopidogrel bioactivation and may explain the lack of association between PON1 genotypes and drug response observed in our study.…”

“…A recent study using PON1-deficient mice, in which platelet reactivity was assessed by PFA-100, showed PON1 deficiency does not influence the antiplatelet action of clopidogrel in mice. 54 These results reinforce the hypothesis that the enzyme is not involved in clopidogrel bioactivation and may explain the lack of association between PON1 genotypes and drug response observed in our study. Allele frequencies for the PON1 Q192R polymorphism were compared to populations of different ethnic backgrounds (Table 3) revealing statistically significant differences between our cohort and specific population of the different ancestries (Caucasian, Asian, and some Latin-American) (P < 0.05).…”