Paraoxonase polymorphism Met-Leu54 is associated with modified serum concentrations of the enzyme. A possible link between the paraoxonase gene and increased risk of cardiovascular disease in diabetes.

Garin, MI; James, Richard; Dussoix, Philippe; Blanché, Hélène; Passa, P; Froguel, P; Ruiz, Juan Carlos

doi:10.1172/jci119134

Cited by 449 publications

(225 citation statements)

References 29 publications

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“…Decreased PON in patients with Type II diabetes and CAD have also been found [44,45]. Polymorphisms within the PON gene that are prevalent in Type II diabetic patients with CAD have been reported [7,46]. These PON polymorphisms result in lower PON activity and are considered to be independent risk factors for CHD in Type II diabetic patients.…”

Section: Discussionmentioning

confidence: 96%

Glycation impairs high-density lipoprotein function

et al. 2000

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Section: Discussionmentioning

confidence: 96%

Glycation impairs high-density lipoprotein function

et al. 2000

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“…Serum PON1 activity is influenced by environmental and genetic factors and varies among individuals in all populations. These variations in PON1 activity are mainly related to the expression of two polymorphisms located in the coding regions of the PON1 gene; Q192R (Q: glutamine, R: arginine) and L55M (L: leucine, M: methionine) [1,9,13,17,23,27]. Subsequent studies on polymorphisms contained in the promoter region of the PON1 locus have shown that the polymorphism located in the promoter region T(-107)C has a dominant effect on PON1 gene expression and enzymatic activity [5,14,22].…”

Section: Introductionmentioning

confidence: 99%

Effect of atorvastatin on paraoxonase1 (PON1) and oxidative status

Nagila

Permpongpaiboon

Tantrarongroj

et al. 2009

Pharmacological Reports

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Abstract:It has been proposed that paraoxonase1 (PON1), a high density lipoprotein (HDL)-associated esterase/lactonase, has antiatherosclerotic properties. The activity of PON1 is influenced by PON1 polymorphisms. However, the influence of PON1 polymorphisms on PON1 activity and oxidative stress in response to lipid-lowering drugs remains poorly understood. The objective of the present study was to investigate the effects of atorvastatin on PON1 activity and oxidative status. The influence of PON1 polymorphisms on PON1 activity and oxidative status in response to atorvastatin treatment was also evaluated. In total, 22 hypercholesterolemic patients were treated with atorvastatin at a dose of 10 mg/day for 3 months. Lipid profile, lipid oxidation markers (malondialdehyde (MDA), conjugated diene (CD), total peroxides (TP)), total antioxidant substance (TAS), oxidative stress index (OSI), and paraoxonase1 activity were determined before and after treatment. L55M, Q192R, and T(-107)C PON1 polymorphisms were also determined. Atorvastatin treatment significantly reduced the levels of total cholesterol (24.5%), low density lipoprotein (LDL) cholesterol (25.4%), triglycerides (24.4%), CD (4.4%), MDA (15.2%), TP (13.0%) and OSI (24.0%), and significantly increased the levels of TAS (27.3%), and PON1 activity (14.0%). Interestingly, the increase in PON1 activity and the reduction in oxidative stress in response to atorvastatin were influenced only by the PON1 T-107C polymorphism. Atorvastatin treatment improved the lipid profile, lipid oxidation, and oxidative/antioxidative status markers including the activity of PON1 towards paraoxon. These beneficial effects may be attributed to the antioxidant properties of statins and the increase in PON1 activity. The increase in PON1 activity was enhanced by the PON1 T-107C polymorphism.

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“…[3][4][5] On the other hand, not only PON1 activity, but also the polymorphism of the PON1 and PON2 genes has been found to be associated with the same cardiovascular risk factors and diseases. [6][7][8] Among the two common genomic variations of the PON1 gene, the codon 148 (Ala→Gly) mutation was reported to be associated with non-insulin-dependent diabetes 21 and might worsen glycaemia and lipidaemia in diabetic patients. The codon 192 mutation of the same gene was associated with the risk of coronary heart disease and had a synergistic effect with the codon 311 (Cys→Ser) polymorphism of another gene, the PON2 from the PON gene family.…”

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confidence: 99%

Codon 311 (Cys → Ser) polymorphism of paraoxonase-2 gene is associated with apolipoprotein E4 allele in both Alzheimer’s and vascular dementias

Janka¹,

Juhász²,

Rimanóczy³

et al. 2002

Mol Psychiatry

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The gene of an esterase enzyme, called paraoxonase (PON, EC.3.1.8.1.) is a member of a multigene family that comprises three related genes PON1, PON2, and PON3 with structural homology clustering on the chromosome 7. 1,2 The PON1 activity and the polymorphism of the PON1 and PON2 genes have been found to be associated with risk of cardiovascular diseases such as hypercholesterolaemia, non-insulin-dependent diabetes, coronary heart disease (CHD) and myocardial infaction. 3-8 The importance of cardiovascular risk factors in the pathomechanism of Alzheimer's disease (AD) and vascular dementia (VD) 9-13 prompted us to examine the genetic effect of PON2 gene codon 311 (Cys→Ser; PON2*S) polymorphism and the relationship between the PON2*S allele and the other dementia risk factor, the apoE polymorphism in these dementias. The PON2*C and PON2*S allele frequencies were similar in both AD (25% and 75%) and VD groups (23% and 77%), respectively, compared with the controls (27% and 73%). The ratio of the PON2*S carriers was significantly higher among the apoE4 allele carrier AD (27%) and VD (25%) groups than in the control (12%). Our results indicate that the PON2*S and apoE4 alleles have interactive effect on the development of the two most common forms of dementias AD and VD, and further support the hypothesis that cardiovascular factors contribute to the development of AD.

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Paraoxonase polymorphism Met-Leu54 is associated with modified serum concentrations of the enzyme. A possible link between the paraoxonase gene and increased risk of cardiovascular disease in diabetes.

Cited by 449 publications

References 29 publications

Glycation impairs high-density lipoprotein function

Glycation impairs high-density lipoprotein function

Effect of atorvastatin on paraoxonase1 (PON1) and oxidative status

Codon 311 (Cys → Ser) polymorphism of paraoxonase-2 gene is associated with apolipoprotein E4 allele in both Alzheimer’s and vascular dementias

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