PON1 (paraoxonase-1) is an HDL (high-density lipoprotein)-associated enzyme capable of hydrolysing diverse substrates from OP (organophosphate) toxins to oxidized phospholipids. As such, it has been linked with both the prevention of OP poisoning and inhibition of atherosclerosis initiated by oxidatively modified LDL (low-density lipoprotein). Mice deficient in PON1 are more susceptible to OP poisoning and oxidative stress and more prone to develop atherosclerosis than their wild-type siblings. There are a number of polymorphisms in the PON1 gene which affect serum PON1 activity and concentration. Many (but not all) studies in human populations have suggested that these polymorphisms may be a risk factor for atherosclerosis. The serum concentration of PON1 across the general population is highly variable and there is some debate as to whether genotype or phenotype (i.e. the quantity or quality of the enzyme) is most accurately associated with risk of disease development. What is clear is that factors influencing serum levels of PON1, be they genetic or environmental, will, in turn, affect the capacity of HDL to protect LDL from oxidation and, consequently, may be linked to atherosclerosis. This review will focus on mechanisms which determine the serum concentration of PON1, including gene expression and genetic polymorphisms, protein secretion and association with HDL, pharmacological and environmental factors.
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November 2004
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Review Article|
October 26 2004
Genetic and environmental factors modulating serum concentrations and activities of the antioxidant enzyme paraoxonase-1 Available to Purchase
Sara P. DEAKIN;
1Clinical Diabetes Unit, Division of Endocrinology, Diabetes and Nutrition, Faculty of Medicine, University Hospital, Geneva, Switzerland
Correspondence: Dr Sara P. Deakin (email [email protected]).
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Richard W. JAMES
Richard W. JAMES
1Clinical Diabetes Unit, Division of Endocrinology, Diabetes and Nutrition, Faculty of Medicine, University Hospital, Geneva, Switzerland
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Publisher: Portland Press Ltd
Received:
June 30 2004
Revision Received:
July 15 2004
Accepted:
August 24 2004
Accepted Manuscript online:
August 24 2004
Online ISSN: 1470-8736
Print ISSN: 0143-5221
The Biochemical Society
2004
Clin Sci (Lond) (2004) 107 (5): 435–447.
Article history
Received:
June 30 2004
Revision Received:
July 15 2004
Accepted:
August 24 2004
Accepted Manuscript online:
August 24 2004
Citation
Sara P. DEAKIN, Richard W. JAMES; Genetic and environmental factors modulating serum concentrations and activities of the antioxidant enzyme paraoxonase-1. Clin Sci (Lond) 1 November 2004; 107 (5): 435–447. doi: https://doi.org/10.1042/CS20040187
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