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Paraoxonase 1 L55M, Q192R and paraoxonase 2 S311C alleles in atherothrombosis

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Abstract

Increased oxidative stress is known to play a role in the pathogenesis of atherosclerosis, and polymorphisms in genes encoding for enzymes involved in modulation of oxidant stress, such as paraoxonases (PONs), provide a potentially powerful approach to study the risk of disease susceptibility. Aim of our study is to investigate the possible association among PONs polymorphisms, clinical and metabolic factors, and atherothrombotic events in an Italian population. We evaluated in 105 subjects, with or without atherosclerotic risk factors, the presence of PON1 L55M, PON1 Q192R, and PON2 S311C genetic variants, as well as lipid profile, the concentration of aminothiols (blood reduced glutathione, plasma total glutathione, homocysteine, cysteine, cysteinyl glycine), and malondialdehyde as markers of lipid peroxidation. Clinical, biochemical, and genetic variables were correlated with a history of atherothrombosis. Previous atherothrombotic events were found in 42 patients (40 %): myocardial infarction in 24, stroke or transient ischemic attack in 18. By multiple logistic regression analysis, hypertension (OR = 5.538; 95 % CI 2.202–13.902, P < 0.001), HDL-cholesterol concentration (OR = 0.947; 95 % CI 0.910–0.985, P = 0.007), and the presence of C allele in PON2 gene (OR = 3.595; 95 % CI 1.247–10.361, P = 0.018) were independently associated with atherothrombotic events. Our study sheds light on the role of PON2 as a possible cofactor in determining the risk of events together with the well-known risk markers HDL-cholesterol and hypertension.

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Acknowledgments

The skillful technical assistance of Salvatore Cassano, Nicoletta Dossena, and Antonella Salcito are gratefully acknowledged. We thank Elisabetta Spagnolo for the excellent technical assistance. This study was partially supported by a Grant from FP7-ICT-2007 project (Grant agreement 224297, ARTreat).

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Authors and Affiliations

  1. CNR Institute of Clinical Physiology, Cardiothoracic and Vascular Department, Niguarda Ca’ Granda Hospital, Milan, Italy

    L. Cozzi, J. Campolo, M. Parolini, R. De Maria & O. Parodi

  2. Laboratory of Medical Genetics, Clinical Chemistry and Clinical Pathology Department, Niguarda Ca’ Granda Hospital, 20162, Milan, Italy

    M. C. Patrosso, A. Marocchi & S. Penco

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  1. L. Cozzi
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  2. J. Campolo
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  3. M. Parolini
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  4. R. De Maria
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  6. A. Marocchi
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  7. O. Parodi
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  8. S. Penco
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Corresponding author

Correspondence to S. Penco.

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L. Cozzi and J.Campolo contributed equally to this study.

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Cozzi, L., Campolo, J., Parolini, M. et al. Paraoxonase 1 L55M, Q192R and paraoxonase 2 S311C alleles in atherothrombosis. Mol Cell Biochem 374, 233–238 (2013). https://doi.org/10.1007/s11010-012-1525-2

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  • DOI: https://doi.org/10.1007/s11010-012-1525-2

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