Project Summary (2000-2006)

Paraoxonase (PON1) is an A-esterase that has been found to display a substrate-dependent polymorphism in humans. Determination of PON1 status (which includes both PON1192 genotype and level of expression) of an individual may allow the use of this enzyme as a biomarker of susceptibility to certain environmentally-induced diseases. The goal of this project is to carry out a series of experiments, the results of which will add important knowledge of PON1 function and modulation, thus increasing its reliability as a marker of susceptibility by better defining variables that affect its use in large epidemiological studies. Because PON1 detoxifies a number of organophosphates and metabolizes bioactive oxidized lipids, studies on PON1 have a direct impact on the susceptibility to pesticide poisoning and to cardiovascular diseases, particularly atherosclerosis. Furthermore, the emerging role of PON1 as an "antioxidant" protein may have importance in certain neuro-degenerative diseases such as Parkinson's disease. Several epidemiological studies have suggested that exposure to pesticides may be a risk factor for Parkinson's disease, and a recent study suggests that the PON1Q192 genotype may also be a risk factor for this disease. Project investigators are confirming and expanding this preliminary observation by determining PON1 status in groups of control and Parkinson's disease patients.