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

Anna I. Kakafika; Stavroula Xenofontos; Vasilis Tsimihodimos; Afroditi P. Tambaki; Evangelia S. Lourida; Rigas Kalaitzidis; Marios A. Cariolou; Moses Elisaf; Alexandros D. Tselepis

Journal of Lipid Research (Oct 2003)

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

Anna I. Kakafika,
Stavroula Xenofontos,
Vasilis Tsimihodimos,
Afroditi P. Tambaki,
Evangelia S. Lourida,
Rigas Kalaitzidis,
Marios A. Cariolou,
Moses Elisaf,
Alexandros D. Tselepis

Affiliations

Anna I. Kakafika: Department of Internal Medicine, Department of Chemistry, University of Ioannina, 45110 Ioannina, Greece; Medical School and Laboratory of Biochemistry, Department of Chemistry, University of Ioannina, 45110 Ioannina, Greece; The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus
Stavroula Xenofontos: Department of Internal Medicine, Department of Chemistry, University of Ioannina, 45110 Ioannina, Greece; Medical School and Laboratory of Biochemistry, Department of Chemistry, University of Ioannina, 45110 Ioannina, Greece; The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus
Vasilis Tsimihodimos: Department of Internal Medicine, Department of Chemistry, University of Ioannina, 45110 Ioannina, Greece; Medical School and Laboratory of Biochemistry, Department of Chemistry, University of Ioannina, 45110 Ioannina, Greece; The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus
Afroditi P. Tambaki: Department of Internal Medicine, Department of Chemistry, University of Ioannina, 45110 Ioannina, Greece; Medical School and Laboratory of Biochemistry, Department of Chemistry, University of Ioannina, 45110 Ioannina, Greece; The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus
Evangelia S. Lourida: Department of Internal Medicine, Department of Chemistry, University of Ioannina, 45110 Ioannina, Greece; Medical School and Laboratory of Biochemistry, Department of Chemistry, University of Ioannina, 45110 Ioannina, Greece; The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus
Rigas Kalaitzidis: Department of Internal Medicine, Department of Chemistry, University of Ioannina, 45110 Ioannina, Greece; Medical School and Laboratory of Biochemistry, Department of Chemistry, University of Ioannina, 45110 Ioannina, Greece; The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus
Marios A. Cariolou: Department of Internal Medicine, Department of Chemistry, University of Ioannina, 45110 Ioannina, Greece; Medical School and Laboratory of Biochemistry, Department of Chemistry, University of Ioannina, 45110 Ioannina, Greece; The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus
Moses Elisaf: Department of Internal Medicine, Department of Chemistry, University of Ioannina, 45110 Ioannina, Greece; Medical School and Laboratory of Biochemistry, Department of Chemistry, University of Ioannina, 45110 Ioannina, Greece; The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus
Alexandros D. Tselepis: Department of Internal Medicine, Department of Chemistry, University of Ioannina, 45110 Ioannina, Greece; Medical School and Laboratory of Biochemistry, Department of Chemistry, University of Ioannina, 45110 Ioannina, Greece; The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus

Journal volume & issue: Vol. 44, no. 10
pp. 1919 – 1926

Abstract

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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.

Published in Journal of Lipid Research

ISSN: 0022-2275 (Print); 1539-7262 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science: Chemistry: Organic chemistry: Biochemistry
Website: https://www.journals.elsevier.com/journal-of-lipid-research

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