Influence of paraoxonase1 Q192R and lifestyle factors on PON1 activity over time in an agricultural population.
Badtke-L; Kelly-KM; Wang-K; Merchant-JA; Ludewig-G
Toxicologist 2012 Mar; 126(Abstract Suppl):105-106
Paraoxonase1 (PON1) was shown to play a major role in susceptibility to adverse health effects from various pesticides and oxidative stress. Gene polymorphisms influence protein concentration and substrate specificity, as do some occupational and lifestyle factors. The goal of this study was to examine the influence of genes, aging, pesticide exposure and lifestyle factors on individual PON1 activities in a potentially at-risk, agricultural population. DNA and, 3 times roughly every 5 years, serum and questionnaire data were gathered from 340 rural Iowans aged 8-91 over the study. PON1 activity was determined using phenyl acetate (PA) and CMPA [4-(Chloromethyl)phenyl acetate] as substrates, and Q192R genotyping was performed using the TaqMan-Applied Biosystems 7900 HT System. Analysis of variance [ANOVA] with repeated-measures did not show the expected decrease in PON1 activity over time with either substrate. With PA significant differences in activity were observed among genotypes and between genders, while with CMPA a significant difference was only seen among genotypes. Canonical discriminant analysis confirmed that the PON1 activity-defined by PA and CMPA substrates-provided good separation of the genotypes at each time point (R-sq range: 0.65-0.73), suggesting approximately 70% of the variation in PON1 activity is explained by the Q192R genotype. ANOVA controlling for gender and genotype found BMI, blood pressure, living or working on a farm, or ever smoking were not significantly associated with variations in PON1 activity, while significant associations were noted between current smoking and CMPA levels, and non-fasting total cholesterol and PA levels. Overall, this study demonstrates that in this agricultural population the individual PON1 levels remained stable over about 15 years, and variation between PON1 activities is largely influenced by genetics.
Agriculture; Agricultural-workers; Oxidative-processes; Agricultural-chemicals; Pesticides; Pesticides-and-agricultural-chemicals; Genetic-factors; Genetics; Protein-chemistry; Proteins; Farmers; Smoking; Serum-cholesterol; Sex-factors; Genes; Age-factors; Employee-exposure; Employee-health;
Author Keywords: PON1; polymorphism; agricultural population
The Toxicologist. Society of Toxicology 51st Annual Meeting and ToxExpo, March 11-15, 2012, San Francisco, California
University of Iowa, Iowa City, Iowa