Relationship of human paraoxonase-1 serum activity and genotype with atherosclerosis in individuals from the Deep South

Abstract

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.

Association of type 2 diabetes mellitus with plasma organochlorine compound concentrations

“…15 The basic model developed here included age, race, BMI (all known factors associated with T2DM), and Air Force base. Despite the association seen for trans-nonachlor and T2DM observed with the univariable modeling, no association was observed when the relevant demographic/clinical factors were adjusted for, indicating that trans-nonachlor was not associated with T2DM independently of the known risk factors.…”

“…Our approach was to identify associations between the presence of T2DM and the presence or concentration of OC compounds, as well as various clinical and demographic factors through multivariable logistic regression modeling, similar to modeling approaches we have used before. 15 This approach has allowed us to identify novel interactions of OC compounds with obesity and with age. We also describe a solid phase extraction method for plasma that is faster and more efficient for extracting these OC compounds from human plasma than the traditional method.…”

Human paraoxonase 1 hydrolysis of nanomolar chlorpyrifos-oxon concentrations is unaffected by phenotype or Q192R genotype

“…As a point of comparison, the activities of these four subsets in hydrolyzing paraoxon and diazoxon were calculated, using the data from the previous study (Coombes et al, 2011) on only the 40 subjects selected to be in the subset for the present study. Serum of subjects homozygous for the PON1 R192 alloform with a high activity phenotype (high RR) hydrolyzed significantly more paraoxon (p<0.001) than the serum of subjects from any of the other groups.…”

“…Subjects of the original study sample were enrolled for blood collection from the clinical practice of Cardiology Associates of North Mississippi, LLC, for the previously described study (Coombes et al ., 2011). Serum was stored at −70°C until analysis of PON1 activity with CPO.…”

“…The present study utilized serum collected previously during a study involving the PON1 192 genotyping and PON1 phenotyping (i.e., activity levels for select substrates) of African American and Caucasian male and female subjects (Coombes et al ., 2011). The PON1 192 genotype was determined using a restriction fragment length polymorphism assay and the PON1 phenotype was assessed with two substrates, paraoxon and diazoxon.…”