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Originally published In Press as doi:10.1194/jlr.M500281-JLR200 on December 3, 2005

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Journal of Lipid Research, Vol. 47, 515-520, March 2006
Copyright © 2006 by American Society for Biochemistry and Molecular Biology

Paraoxonase-1 and serum concentrations of HDL-cholesterol and apoA-I

Marie-Claude Blatter Garin1, Xenia Moren and Richard W. James2

Clinical Diabetes Unit, Division of Endocrinology, Diabetes, and Nutrition, Medical Faculty, University Hospital, 1211 Geneva 14, Switzerland

Published, JLR Papers in Press, December 3, 2005.

1 Present address of M-C. Blatter Garin: Swiss Institute of Bioinformatics, University Medical Center, Medical Faculty, University of Geneva, Geneva, Switzerland.

2 To whom correspondence should be addressed. e-mail: richard.james{at}hcuge.ch

Paraoxonase-1 (PON1) and HDL are tightly associated in plasma, and this is generally assumed to reflect the need for the enzyme to associate with a hydrophobic complex. The association has been examined in coronary cases and age-matched controls. Highly significant (P < 0.0001), positive associations were observed between PON1 activities and concentrations and HDL-cholesterol and apolipoprotein A-I (apoA-I) concentrations in cases and controls. Corrected slopes were significantly different in cases (cases vs. controls: arylesterase, r = 0.19 vs. 0.38, P < 0.02 for apoA-I and r = 0.15 vs. 0.34, P < 0.02 for HDL-cholesterol) such that if PON1 should influence serum HDL, it would be less effective in coronary cases. When examined as a function of the PON1 gene promoter polymorphism C–107T, highly significant differences (P < 0.001) in HDL-cholesterol and apoA-I were observed between genotypes for controls, with high expresser alleles having the highest HDL concentrations. This relationship was lost in cases with coronary disease. The coding region polymorphisms Q192R and L55M of the PON1 gene showed no association with HDL. The promoter polymorphism was an independent determinant of HDL concentrations in multivariate analyses. These data are consistent with an impact of PON1 on plasma concentrations of HDL, with detrimental modifications to the relationship in coronary cases.

Supplementary key words atherosclerosis • oxidative stress • low density lipoprotein • high density lipoprotein • apolipoprotein A-I


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