Genetic polymorphisms of paraoxonase 1 and susceptibility to atherogenesis

Abstract

Paraoxonase 1 (PON1) is a multifunctional enzyme associated with high-density lipoprotein particles (HDL). It is a cellular antioxidant that hydrolyses oxidized macromolecules, especially low-density lipoproteins (ox-LDL). Because increased oxidative stress is believed to play a crucial role in the initiation and propagation of atherosclerosis, coding (Q192R and L55M) and promoter (C(-107)T) region polymorphisms of pon1 gene, that are responsible for catalytic efficiency, activity and the level of the enzyme, have been of great interest as a potential markers of susceptibility for atherogenesis. The aim of the study was to assess possible association between these pon1 gene variants and clinical manifestations of the atherosclerosis and oxidative stress. A total of 60 angiographically documented patients with manifested atherosclerotic disease and 100 control individuals were analyzed. Genomic DNA was isolated from the peripheral blood cells and genotyping was performed using polymerase chain reaction followed by the restriction fragment length polymorphism (PCR-RFLP) analysis. No significant difference in allele and genotype frequencies of all three examined polymorphisms was found between the atherosclerotic patients and healthy controls. The obtained results could not support an association of pon1 gene variants with the oxidative stress and atherogenesis. These polymorphisms cannot be considered risk factors of atherosclerosis in Serbian population. A larger study is required in order to establish possible contribution of pon1 variants to atherosclerosis-related cardiovascular diseases.