Biochemical, Environmental, and Genetic Factors Associated with Paraoxonase (PON1) Activity

Abstract

Paraoxonase (PON1, EC 3.1.8.1) is tightly linked to high-density lipoprotein (HDL) and shows significant correlation with apo AI concentrations. It plays an important role in functions such as protection against vascular disease (e.g., atherosclerosis) through its inhibition of low-density lipoprotein (LDL) oxidation and detoxification of organophosphorus compounds by hydrolyzing the bioactive oxons (Mackness et al. 1991). The activity of PON1 is modulated by genetic and environmental factors. Two coding region polymorphisms of the PON1 gene result in amino acid substitutions at position 192 (PON1 Q192R, glutamine to arginine) and at position 55 (PON1 L55 M, leucine to methionine). PON1 Q192R has been reported to account for 73–76% of the variation in hydrolysis activity of paraoxon (paraoxonase activity) and 12–25% of the variation in activity for the hydrolysis of diazoxon (diazonase activity) in vitro (Jarvik et al. 2000). The L55 M polymorphism also contributes to PON1 protein stability and activity (Leviev et al. 2001). PON1 polymorphisms have been studied in many populations of the world; the frequency of the low-activity