J. Lipid Res.
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Originally published In Press as doi:10.1194/jlr.M300129-JLR200 on July 16, 2003

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Journal of Lipid Research, Vol. 44, 1919-1926, October 2003
Copyright © 2003 by American Society for Biochemistry and Molecular Biology

The PON1 M55L gene polymorphism is associated with reduced HDL-associated PAF-AH activity

Anna I. Kakafika*, Stavroula Xenofontos§, Vasilis Tsimihodimos*, Afroditi P. Tambaki{dagger}, Evangelia S. Lourida{dagger}, Rigas Kalaitzidis*, Marios A. Cariolou§, Moses Elisaf* and Alexandros D. Tselepis1,{dagger}

* Department of Internal Medicine, Department of Chemistry, University of Ioannina, 45110 Ioannina, Greece
{dagger} Medical School and Laboratory of Biochemistry, Department of Chemistry, University of Ioannina, 45110 Ioannina, Greece
§ The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus

1 To whom correspondence should be addressed. e-mail: atselep{at}cc.uoi.gr

The platelet-activating factor acetylhydrolase activity associated with high density lipoprotein (HDL-PAF-AH) may substantially contribute to the antioxidant, anti-inflammatory, and overall antiatherogenic effects of HDL. 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. 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 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 M 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 HDL-PAF-AH activity 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 in protecting LDL against lipid peroxidation.

Supplementary key words high density lipoprotein • platelet-activating factor acetylhydrolase • paraoxonase-1 • PON1 polymorphisms • platelet-activating factor acetylhydrolase polymorphisms


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