Human serum paraoxonase (PON1) has been implicated to play an important role in cardiovascular disease and diabetes. Low PON1 activity and/or concentration has been shown in oxidative stress-associated processes such as dyslipidemia, diabetes mellitus, smoking, degree of insulin resistence. PON1 is a calcium-dependent esterase closely associated with the high-density lipoprotein (HDL) subfraction that contains apolipoprotein AI in human serum. Several lines of evidence are emerging that suggest that HDL can prevent oxidation of low-density lipoprotein (LDL) and that some oxidized LDL phospholipids are physiological substrates for serum PON1. The PON1 gene contains several polymorphisms in both the coding and the promoter regions. Many (but not all) studies in human populations have suggested that these polymorphisms may be a risk factor for CHD, diabetes and complications of DM. The serum concentration of PON1 across the general population is highly variable and there is a lot of studies focusing on the role of genotype and phenotype and whether polymorphisms (SNP) or the quantity and/or quality of the enzyme is most accurately associated with the risk of disease development. This review focuses on mechanisms which determine the serum PON1 status, including gene expression and genetic polymorphisms, protein secretion and association with HDL, pharmacological and environmental factors.

        Key words: paraoxonase, polymorphisms, PON1 activity, concentration, modulating factors.