Abstract
HDL-associated paraoxonase 1 (PON1) activity has been consistently associated with cardiovascular and other diseases. Vitamins C and E intake have previously been positively associated with PON1 in a subset of the Carotid Lesion Epidemiology and Risk (CLEAR) cohort. The goal of this study was to replicate these findings and determine whether other nutrient intake affected PON1 activity. To predict nutrient and mineral intake values, 1,402 subjects completed a standardized food frequency survey of their dietary habits over the past year. Stepwise regression was used to evaluate dietary and covariate effects on PON1 arylesterase activity. Five dietary components, cholesterol (P < 2.0 × 10(-16)), alcohol (P = 8.51 × 10(-8)), vitamin C (P = 7.97 × 10(-5)), iron (P = 0.0026), and folic acid (0.037) were independently predictive of PON1 activity. Dietary cholesterol was positively associated and predicted 5.5% of PON1 activity, second in variance explained. This study presents a novel finding of dietary cholesterol, iron, and folic acid predicting PON1 activity in humans and confirms prior reported associations, including that with vitamin C. Identifying and understanding environmental factors that affect PON1 activity is necessary to understand its role and that of HDL in human disease.
Highlights
High density lipoprotein (HDL)-associated paraoxonase 1 (PON1) activity has been consistently associated with cardiovascular and other diseases
Inactivation of PON1 reduced the ability of HDL to Abbreviations: arylesterase activity measured by degradation of phenylacetate (AREase), PON1 arylesterase enzyme activity; AIC, Akaike’s information criterion; CAAD, carotid artery disease; CHD, coronary heart disease; CLEAR, Carotid Lesion Epidemiology and Risk cohort; DZOase, PON1 diazoxon hydrolysis; POase, PON1 paraoxon hydrolysis; PON, paraoxonase, single nucleotide polymorphisms (SNP), single nucleotide polymorphism
Of the dietary and plasma lipid measures, vitamin E was correlated with folic acid (r = 0.53) and vitamin C (r = 0.61), and vitamin C was associated with folic acid (r = 0.50), with P < 0.001 for all three correlations
Summary
HDL-associated paraoxonase 1 (PON1) activity has been consistently associated with cardiovascular and other diseases. This work utilized resources of SeattleSNPs; NHLBI Program for Genomic Applications, SeattleSNPs, Seattle, WA (http://pga.gs.washington.edu) Past work in this cohort was supported in part by VA Puget Sound Health Care System, Seattle, Washington, including the Veterans Affairs Epidemiology Research and Information Center Program (award CSP-701S). A recent large randomized clinical trial did not show a benefit of niacin in preventing adverse cardiovascular outcomes, despite improved levels of HDL-C and triglycerides in the treatment group [6] These results refocus attention on the many aspects of HDL biology that are not captured by serum measurements of HDL, such as its paraoxonase 1 (PON1) activity, which itself is inversely associated with cardiovascular and other human diseases. PON1 activity appears to plays a role in maintaining the endothelial-atheroprotective effects of HDL [16]
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