OBJECTIVE
Paraoxonase 1 (PON1) is synthesized in the liver and bound to high density lipoprotein (HDL) particles in blood. PON1 protects against the development of atherosclerosis by metabolizing pro-atherogenic oxidized lipids. The Southeastern United States (excluding Florida) has the country's highest age-adjusted mortality rate from cardiovascular disease. The current study determines the association of PON1 status with atherosclerosis (ATH) in individuals from the Southeastern United States.
METHODS
Eighty African Americans (40 male, 40 female) and 120 Caucasians (60 male, 60 female) were enrolled from a cardiology practice in northeastern Mississippi. Serum PON1 activities were determined using diazoxon, paraoxon, and phenyl acetate (PhAc) as substrates. The PON1192 genotype of each individual was also determined. A multivariable logistic regression model was developed to identify the associations of clinical characteristics, serum PON1 activity, and PON1192 genotype of the study population with ATH.
RESULTS
A core model consisting of age, gender, history of smoking, hypertension, and LDL-cholesterol group was constructed. The maximum-rescaled generalized r2 value for the core model was 0.35. Addition of PON1 activity assessed by PhAc hydrolysis was the only measure of PON1 enzymatic activity to add significant information to the core model (p= 0.0317) with the maximum-rescaled generalized r2 value increasing to 0.37. Increasing PON1 activity was associated with decreased odds of ATH. The PON1192 genotype was not significantly associated with ATH.
CONCLUSIONS
Increasing PON1 activity assessed by the hydrolysis of PhAc is associated with decreased odds of ATH in a group of African American and Caucasian Southerners.
The organophosphorus insecticide chlorpyrifos has been widely used. Its active metabolite chlorpyrifos-oxon (CPO) is a potent anticholinesterase and is detoxified by paraoxonase-1 (PON1). PON1 activity is influenced by numerous factors including a Q192R polymorphism. Using forty human blood samples bearing homozygous genotypes and either high or low activity phenotypes (as determined by high concentration assays of paraoxon and diazoxon hydrolysis) the serum PON1 hydrolysis of high (320 μM) and low (178 nM) CPO concentrations was assessed using direct or indirect spectrophotometric methods, respectively. PON1 activity at high CPO concentration reflected the phenotype and genotype differences; subjects with the high activity phenotype and homozygous for the PON1R192 alloform hydrolyzed significantly more CPO than subjects with the low activity phenotype and/or PON1Q192 alloform (High RR=11023±722, Low RR=9467±798, High QQ=8809±672, Low QQ=6030±1015 μmoles CPO hydrolyzed/min/L serum). However, PON1 hydrolysis of CPO at the lower, more environmentally relevant concentration showed no significant differences between the PON1192 genotypes and/or between high and low activity phenotypes (High RR=231±27, Low RR=219±52, High QQ=193±59, Low QQ=185±43 nmoles CPO/min/L serum). Low CPO concentrations were probably not saturating, so PON1 did not display maximal velocity and the PON1 genotype/phenotype might not influence the extent of metabolism at environmental exposures.
This paper describes a study of the informational efficiency of the thoroughbred horse racing market in Australia. It is based on the theory of stock market efficiency which explains the process by which information becomes reflected in share prices. In this paper, the theory is applied to the thoroughbred horse racing market to determine the predictive accuracy of alternative informative sources. The results obtained from the study are consistent with the underlying theory:(i) aggregated information (as reflected in a consensus of opinions) is a more accurate prediction of success than less information (as reflected in individual opinions), and;(ii) the most recent information (as reflected in race-time betting odds, known as starting prices) has greater predictive ability than less recent information (as reflected in an earlier consensus of opinions).The study examines predictive accuracy in a gambling context, but does not consider the profitability of alternative prediction processes.
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