Regulation of Serum Paraoxonase Activity by Genetic, Nutritional, And Lifestyle Factors in the General Population (Lipids, Lipoproteins, And Cardiovascular Risk Factors‪)‬

Paraoxonase (PON1) is a calcium-dependent esterase that circulates in plasma associated with HDL (1) and contributes to the protective effect of this lipoprotein on LDL oxidation (1-6). Some authors have extended this suggested antioxidant role of PON1 to a general prevention of peroxidative damage to cell membranes (7,8). However, the enormous variation in serum PON1 activity (~40-fold) observed among individuals (9) complicates its clinical interpretation. This variation can be explained by both genetic and environmental influences. Polymorphisms in the promoter and coding regions of the PON1 gene are the main determinants of its expression and the enzymatic activity (10-14), but serum PON1 activity can be modulated by several environmental factors. Pathologic states such as renal disease, diabetes mellitus, cardiovascular disease, and liver cirrhosis are associated with decreased PON1 activity [reviewed in Ref. (15)], and various dietary and lifestyle factors have been reported to influence serum PON1 activity. Tobacco smoking has been associated with reduced PON1 activity and concentrations in patients with coronary artery disease (16), and extracts of cigarette smoke inhibited PON1 activity in vitro (17). Pharmacologic therapy with simvastatin (18) and hormone replacement therapy (19), on the other hand, have been reported to increase serum PON1 activity.