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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 is bound to high-density lipoprotein particles in blood. PON1 protects against the development of atherosclerosis by metabolizing proatherogenic-oxidized lipids. The Southeastern USA (excluding Florida) has the country's highest age-adjusted mortality rate of cardiovascular disease. This study determines the association of PON1 status with atherosclerosis in individuals from the Southeastern USA. METHODS:Eighty African Americans (40 men, 40 women) and 120 Caucasians (60 men, 60 women) were enrolled from a cardiology practice in Northeastern Mississippi. Serum PON1 activities were determined using diazoxon, paraoxon, and phenyl acetate (PhAc) as substrates. The PON1(192) 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 PON1(192) genotype of the study population with atherosclerosis. RESULTS:A core model consisting of age, sex, history of smoking, hypertension, and low-density lipoprotein-cholesterol group was constructed. The maximum-rescaled generalized r(2) 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 r(2) value increasing to 0.37. Increasing PON1 activity was associated with decreased odds of atherosclerosis. The PON1(192) genotype was not significantly associated with atherosclerosis. CONCLUSION:Increasing PON1 activity assessed by the hydrolysis of PhAc is associated with decreased odds of atherosclerosis in a group of African American and Caucasian Southerners.

journal_name

Pharmacogenet Genomics

journal_title

Pharmacogenetics and genomics

authors

Coombes RH,Crow JA,Dail M,Chambers HW,Wills RW,Barry D. Bertolet for CARe.,Chambers JE

doi

10.1097/FPC.0b013e32834cebc6

subject

Has Abstract

pub_date

2011-12-01 00:00:00

pages

867-875

issue

eissn

1744-6872

issn

1744-6880

journal_volume

pub_type

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