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Originally published In Press as doi:10.1194/jlr.M400489-JLR200 on July 1, 2005

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Journal of Lipid Research, Vol. 46, 1888-1895, September 2005
Copyright © 2005 by American Society for Biochemistry and Molecular Biology

The correlation of paraoxonase (PON1) activity with lipid and lipoprotein levels differs with vascular disease status

Laura S. Rozek*,{dagger}, Thomas S. Hatsukami{dagger}{dagger}, Rebecca J. Richter{dagger}, Jane Ranchalis{dagger}, Karen Nakayama{dagger}, Laura A. McKinstry{dagger}, David A. Gortner§§, Edward Boyko{dagger}{dagger}, Gerard D. Schellenberg§,{dagger}{dagger}, Clement E. Furlong{dagger},** and Gail P. Jarvik1,{dagger},**

* Department of Internal Medicine, University of Michigan, Ann Arbor, MI
{dagger} Department of Medicine, Divisions of Medical Genetics, University of Washington, Seattle, WA
§ Neurology, University of Washington, Seattle, WA
** Department of Genome Sciences, University of Washington, Seattle, WA
{dagger}{dagger} Puget Sound Veterans Affairs Health Care Systems, Seattle, WA
§§ General Internal Medicine, Virginia Mason Medical Center, Seattle, WA

Published, JLR Papers in Press, July 1, 2005. DOI 10.1194/jlr.M400489-JLR200

1 To whom correspondence should be addressed.pair{at}u.washington.edu

in re-

Paraoxonase (PON1) is an HDL-associated enzyme. Low PON1 activity predicts vascular disease status and is a more reliable predictor of vascular disease than are functional PON1 genotypes. There is evidence that the relationship of PON1 to vascular disease is, in part, due to its antioxidant activity. However, the physical relationship of PON1 with HDL and the existence of cholesterol pathway regulatory elements at the PON1 locus suggest a further relationship of PON1 with lipoproteins, which may contribute to its role in vascular disease. We investigated the relationship of PON1 activity and genotype to lipid-related traits in 91 Caucasian men with severe carotid artery disease and 184 without vascular disease who were not on lipid-lowering medications. Prior studies of PON1 relationship to lipids have not stratified by disease status..

We found that PON1 activity was correlated with HDL traits in controls and with LDL- and VLDL-related traits in cases. We hypothesize differences in the joint regulation of PON1 and lipoproteins in cases and controls.

Supplementary key words paraoxonase • lipoprotein • carotid artery disease • apolipoprotein A-I • transcription


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