Individual variation in paraoxonase 1 activity in human serum over time.
Badtke-L; Stromquist-A; Merchant-J; Ludewig-G
Toxicologist 2010 Mar; 114(1):78
Paraoxonase 1 (PON1) is a serum glycoprotein capable of hydrolyzing many pesticides. There is a substantial variation among individuals within a population due to genetic and environmental factors, including the Q192R polymorphism, which affect the efficiency of substrate hydrolysis. Low PON1 activity levels have been associated with increased risk for atherosclerosis and other disorders. It has been shown that PON1 levels appear to be lower in older populations, but no known study has measured serum PON1 activity levels in the same individuals over time. A prospective study is underway to determine if individual serum PON1 levels vary significantly over a time span of about 15 years and which changes in lifestyle, diet, or occupational exposure factors may influence PON1 levels. In a pilot study, 30 rural Iowan males ages 44-73 at the study onset, about half farmers, were evaluated. Serum samples had been taken since 1994 roughly every 5 years and stored at - 80°C, making three samples available from each individual. PON1 activity and Q192R phenotype were determined using phenyl acetate and CMPA [4- (Chloromethyl)phenyl acetate] as substrates. Based on the assay results, all three phenotypes are represented in the cohort. With phenyl acetate and CMPA, 53% and 43% of subjects, respectively, did not show the expected decreased PON1 levels with age. This difference in substrate sensitivity may be due to the lower enzyme specificity of phenyl acetate. This pilot study did not conclusively confirm the assumed age-related decrease in PON1 levels at the individual level. Increasing the number of participants and including dietary, health, and pesticide exposure data from the accompanying questionnaires of this ongoing large population study will allow us to identify genetic and environmental risk factors for low PON1 status, the role of pesticide exposure, and allow us to counsel the most at-risk subgroup about their individual pesticide vulnerability.
Age-factors; Biological-effects; Cell-biology; Cellular-reactions; Chemical-hypersensitivity; Chemical-properties; Chemical-reactions; Environmental-exposure; Environmental-factors; Exposure-assessment; Exposure-levels; Exposure-methods; Genetic-factors; Genetics; Laboratory-animals; Laboratory-testing; Molecular-biology; Particle-aerodynamics; Particulate-dust; Particulates; Pesticides; Pesticides-and-agricultural-chemicals; Questionnaires; Respiratory-hypersensitivity; Respiratory-irritants; Risk-analysis; Sex-factors; Statistical-analysis; Toxic-effects
The Toxicologist. Society of Toxicology 49th Annual Meeting and ToxExpo, March 7-11, 2010, Salt Lake City, Utah
University of Iowa, Iowa City, Iowa