Review

Pharmacogenetics of paraoxonase activity: elucidating the role of high-density lipoprotein in disease

Departments of Genome Sciences & Medicine (Division of Medical Genetics), University of Washington School of Medicine, Box 357720, University of Washington, Seattle, WA 98195-7720, USA

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Judit Marsillach

Departments of Genome Sciences & Medicine (Division of Medical Genetics), University of Washington School of Medicine, Box 357720, University of Washington, Seattle, WA 98195-7720, USA

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Clement E Furlong

Departments of Genome Sciences & Medicine (Division of Medical Genetics), University of Washington School of Medicine, Box 357720, University of Washington, Seattle, WA 98195-7720, USA

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Gail P Jarvik

* Author for correspondence

Departments of Genome Sciences & Medicine (Division of Medical Genetics), University of Washington School of Medicine, Box 357720, University of Washington, Seattle, WA 98195-7720, USA.

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Email the corresponding author at pair@u.washington.edu

Published Online:11 Sep 2013https://doi.org/10.2217/pgs.13.147

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Abstract

PON1 is a key component of high-density lipoproteins (HDLs) and is at least partially responsible for HDL’s antioxidant/atheroprotective properties. PON1 is also associated with numerous human diseases, including cardiovascular disease, Parkinson’s disease and cancer. In addition, PON1 metabolizes a broad variety of substrates, including toxic organophosphorous compounds, statin adducts, glucocorticoids, the likely atherogenic L-homocysteine thiolactone and the quorum-sensing factor of Pseudomonas aeruginosa. Numerous cardiovascular and antidiabetic pharmacologic agents, dietary macronutrients, lifestyle factors and antioxidant supplements affect PON1 expression and enzyme activity levels. Owing to the importance of PON1 to HDL function and its individual association with diverse human diseases, pharmacogenomic interactions between PON1 and the various factors that alter its expression and activity may represent an important therapeutic target for future investigation.

Keywords:

Papers of special note have been highlighted as: ▪ of interest ▪▪ of considerable interest

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Vol. 14, No. 12

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Published online 11 September 2013

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Financial & competing interests disclosure

This work was funded in part by NIH RO1 HL67406, R01 ES09883 and P42 ES04696, and a State of Washington Life Sciences Discovery Award (265508) to the Northwest Institute of Genetic Medicine. J Marsillach was partially supported by a Beatriu de Pinós postdoctoral fellowship (2008 BP A 00166) from Comissionat per a Universitats i Recerca del Departament d’Innovació, Universitats I Empresa, Catalunya, Spain. DS Kim was supported in part by the Sarnoff Cardiovascular Research Fellowship for Medical Students, the Benjamin and Margaret Hall Endowed Fellowship in Genome Sciences and NIH 5T31HG000035-18 and 1F31MH101905-01. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

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