The correlation of paraoxonase (PON1) enzyme activities with plasma lipid and lipoprotein levels differs for subjects with and without vascular disease

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

Department of Medicine and Medical Genetics, University of Washington, Seattle, Seattle, WA 98195-7720

Corresponding Author: pair{at}u.washington.edu

Paraoxonase (PON1) is an HDL-associated enzyme. Low PON1 activity predicts vascular disease status and is a more reliable predictor of vascular disease than 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 existence of cholesterol pathway regulatory elements at the PON1 locus suggests 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 with 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.

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