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.
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