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Papers In Press, published online ahead of print July 16, 2003
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Department of Chemistry, University of Ioannina, Ioannina 45110
Corresponding Author: atselep{at}cc.uoi.gr
Low plasma levels of high-density lipoprotein (HDL) represent an independent risk factor for coronary heart disease (CHD). Several lines of evidence suggest that the HDL-associated platelet-activating factor acetylhydrolase (HDL-PAF-AH) activity may substantially contribute to the antioxidant and anti-inflammatory effects of HDL, thus this activity may be an important component of the multiple mechanisms by which HDL slows the progression of atherosclerosis. Two enzymes associated with HDL express PAF-AH catalytic activity, PAF-AH itself and paraoxonase-1 (PON1). The relative contribution of these enzymes in the expression of PAF-AH activity on HDL remains to be established. In the present study we investigated whether the PON1 polymorphisms (M55L and Q192R) or the PAF-AH polymorphism V379A could affect the PAF-AH activity associated with HDL in both normolipidemic and dyslipidemic (Type IIA and IIB) populations. We show for the first time that among the polymorphisms studied, the PON1 M55L polymorphism significantly affects the HDL-PAF-AH activity in all studied groups, the PON1 L55L individuals having lower enzyme activity compared to those having 1 and 2 M alleles. No differences in the HDL content concerning the major apolipoprotein and lipid constituents were observed between individuals carrying the PON1 L55L and those with the M55M polymorphism. Our results provide evidence that PON1 significantly contributes to the pool of PAF-AH activity associated with HDL in human plasma, and suggest that the low PAF-AH activity in HDL carrying the PON1 L alloenzyme may be an important factor contributing to the low efficiency of this HDL to protect LDL against lipid peroxidation.
Revised on July 8, 2003
Accepted on July 14, 2003
The PON1 M55L gene polymorphism is associated with reduced HDL-associated PAF-AH activity in normolipidemic and dyslipidemic populations
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