Pharmacogenetics of paraoxonase activity: elucidating the role of high-density lipoprotein in disease.

PON1 is a key component of high-density lipoproteins (HDLs) and is at least partially responsible for HDL's antioxidant/atheroprotective properties. PON1 is also associated with numerous human diseases, including cardiovascular disease, Parkinson's disease and cancer. In addition, PON1 metabolizes a broad variety of substrates, including toxic organophosphorous compounds, statin adducts, glucocorticoids, the likely atherogenic L-homocysteine thiolactone and the quorum-sensing factor of Pseudomonas aeruginosa. Numerous cardiovascular and antidiabetic pharmacologic agents, dietary macronutrients, lifestyle factors and antioxidant supplements affect PON1 expression and enzyme activity levels. Owing to the importance of PON1 to HDL function and its individual association with diverse human diseases, pharmacogenomic interactions between PON1 and the various factors that alter its expression and activity may represent an important therapeutic target for future investigation.