Associations between HDL oxidation and paraoxonase-1 and paraoxonase-1 gene polymorphisms in families affected by familial combined hyperlipidemia

Abstract

Background and aim: It has been shown in vitro that the HDL-bound enzyme paraoxonase-1 (PON1) protects LDL against oxidation, and PON1 and PON1 gene polymorphisms may affect the oxidation of HDL particles. The aim of this study was to investigate the associations between in vitro HDL oxidation parameters, endogenous PON1 and PON1 genotypes in families affected by asymptomatic FCHL.

Methods and results: Serum arylesterase (ARE) and PON1 activities, PON1 mass, PON1 genotypes and the kinetics of CuSO4-induced HDL oxidation in vitro were measured in 150 members of FCHL families free of clinical CAD. At univariate analysis, log PON1/apoA-I and the PON1 mass/apoA-I ratio significantly correlated with lag time, maximum diene formation and the propagation rate. The oxidation parameters also correlated with PON1 genotypes. Multivariate analysis showed that the associations between PON1 mass/unit apoA-I and the oxidation parameters were independent of the other variables. The lag time of HDL oxidation was also associated with the PON1 genotype 192QR.

Conclusions: Endogenous PON1 may have protective effects on the different stages of HDL oxidation in the members of families affected by FCHL. This protective effect is independent of other biochemical factors, but may be influenced by the PON1 gene polymorphism. The endogenous PON1 content of HDL seems to be an important determinant of the anti-atherogenicity of this lipoprotein.