Interrelationship of serum paraoxonase activity and paraoxonase genetic variants on atherosclerosis risk

Abstract

Paraoxonase (PON1) is a calcium-dependent esterase, closely associated with high-density lipoprotein (HDL)-containing apolipoprotein AI, that has been reported to confer antioxidant properties on HDL by decreasing the accumulation of lipid peroxidation products. PON1 activity is under genetic and environmental regulation and appears to vary widely among individuals and populations. PON1 enzyme activity for paraoxon as a substrate is modulated by a number of polymorphisms at the PON1 locus in humans. One of them is the PON1-192 genetic polymorphism that comprises PON1 Q, an isoform which has a glutamine at position 192, and shows a low activity towards paraoxon hydrolysis, while the high paraoxon-activity PON1 R isoform contains an arginine at position 192. The association of PON1 activity levels with atherosclerosis in human, animal and in vitro studies is consistent and exciting. Therefore, there is an obvious need to know whether environmental factors can influence serum PON1. The genetic association studies for PON1 and atherosclerosis are less consistent, since the PON1 polymorphisms probably only produce an effect on coronary heart disease risk in particular subgroups of subjects in the presence of additional factors. It is particularly important to study gene-environmental interactions that may modulate phenotypic expression of PON1 in different populations.