Effects of paraoxonase activity and gene polymorphism on coronary vasomotion

BACKGROUND: Paraoxonase 1 [PON1] is recognized as a protective enzyme against LDL oxidation, and PON1 polymorphism has been described as a factor influencing coronary heart disease [CHD] free survival. As coronary vasoreactivity is a surrogate of future cardiovascular events, we aimed at assessing the respective effect of the PON1 genotype and activity on coronary vasoreactivity in a population of type 2 diabetic patients. METHODS: Nineteen patients with type 2 diabetes mellitus underwent (82)Rb cardiac PET/CT to quantify myocardial blood flow [MBF] at rest, during cold pressor testing [CPT], and during adenosine-induced hyperaemia to compute myocardial flow reserve [MFR]. They were allocated according to Q192R and L55M polymorphisms into three groups (wild-type and LM/QR heterozygotes, MM homozygotes, and RR homozygotes) and underwent a measurement of plasmatic PON1 activity. Relations between rest-MBF, stress-MBF, MFR, and MBF response to CPT and PON1 genotypes and PON1 activity were assessed using Spearman's correlation and multivariate linear regression analysis. RESULTS: Although PON1 activity was significantly associated with PON1 polymorphism (p < 0.0001), there was no significant relation between the PON1 genotypes and the rest-MBF, stress-MBF, or MBF response to CPT (p ≥ 0.33). The PON1 activity significantly correlated with the HDL plasma level (ρ = 0.63, p = 0.005), age (ρ = -0.52, p = 0.027), and MFR (ρ = 0.48, p = 0.044). Moreover, on multivariate analysis, PON1 activity was independently associated with MFR (p = 0.037). CONCLUSION: Our study supports an independent association between PON1 activity and MFR. Whether PON1 contributes to promote coronary vasoreactivity through its antioxidant activity remains to be elucidated. This putative mechanism could be the basis of the increased risk of CHD in patients with low PON1 activity.