Effect of PON1 polymorphism on HDL antioxidant potential is blunted with aging

Abstract

Paraoxonase1 is a HDL-associated enzyme, which is responsible for their antioxidant property. This study was aimed to investigate the effect of PON1 [Q192R] and [L55M] genotypes on susceptibility of LDL and HDL to lipid peroxidation and on antioxidant activity of HDL as a function of aging. Seventy-eight healthy subjects distributed in two age groups, young (20-30 years) and elderly (60-89 years) were recruited. PON1 activities and genotype polymorphisms were determined for each subject. LDL and HDL susceptibility to lipid peroxidation was evaluated by the measure of lag-phase (LP) for conjugated diene formation. HDL antioxidant property was evaluated by the measure of their capacity to protect LDL against lipid peroxidation. Our results show that LP for LDL and HDL peroxidation decreased with age of donors. Moreover, PON1 genotypes affect significantly the susceptibility of LDL and HDL to lipid peroxidation. Furthermore, basal- and salt-stimulated paraoxonase as well arylesterase activities were significantly reduced in elderly compared to young subjects. These results show a beneficial effect of PON1 towards susceptibility of HDL to oxidation as well to their antioxidant effect. However, this PON1 protective effect seems to be blunted with advancing age. Altogether our results suggest that the decrease in the PON1 protective effect with aging may contribute to the acceleration of the atherosclerosis process in elderly.