Polymorphisms in the human paraoxonase (PON1) promoter

Brophy, Victoria H.; Hastings, Michele D.; Clendenning, James B.; Richter, Rebecca J.; Jarvik, Gail P.; Furlong, Clement E.

doi:10.1097/00008571-200102000-00009

Cited by 170 publications

(114 citation statements)

References 44 publications

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“…Although PON1 activity was measured in a subgroup of subjects, PON1 polymorphisms influenced at least one of the two measured activities, in agreement with published data (19). PON1 activity was higher in the abnormal PFT group but did not achieve statistical significance.…”

Section: Discussionsupporting

confidence: 88%

Association Between p.Leu54Met Polymorphism at the Paraoxonase-1 Gene and Plantar Fascia Thickness in Young Subjects With Type 1 Diabetes

et al. 2008

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OBJECTIVE -In type 1 diabetes, plantar fascia, a collagen-rich tissue, is susceptible to glycation and oxidation. Paraoxonase-1 (PON1) is an HDL-bound antioxidant enzyme. PON1 polymorphisms have been associated with susceptibility to macro-and microvascular complications. We investigated the relationship between plantar fascia thickness (PFT) and PON1 gene variants, p.Leu54Met, p.Gln192Arg, and c.-107CϾT, in type 1 diabetes. RESEARCH DESIGN AND METHODS-This was a cross-sectional study of 331 adolescents with type 1 diabetes (162 male and 169 female). PFT was assessed by ultrasound, PON1 was assessed by genotyping with PCR and restriction fragment-length polymorphism, and serum PON1 activity was assessed by rates of hydrolysis of paraoxon and phenylacetate.RESULTS -Median (interquartile range) age was 15.4 (13.5-17.3) years, and diabetes duration was 7.6 (4.9 -10.6) years. The distribution of p.Leu54Met genotypes was LL 135 (40.8%), ML 149 (45%), and MM 47 (14.2%). PFT was abnormal (Ͼ1.7 mm) in 159 adolescents (48%). In multivariate analysis, predictors of abnormal PFT were ML/LL versus MM p. CONCLUSIONS -Thickening of the plantar aponeurosis occurs predominantly in overweight and male adolescents with type 1 diabetes. The MM genotype at PON1 p.Leu54Met is associated with a reduced risk of abnormal PFT.

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Section: Discussionsupporting

confidence: 88%

Association Between p.Leu54Met Polymorphism at the Paraoxonase-1 Gene and Plantar Fascia Thickness in Young Subjects With Type 1 Diabetes

et al. 2008

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“…The relationship between genotype and CHD risk is becoming ever more complicated with the emerging importance of promoter polymorphisms, some of which are in linkage disequilibrium with the coding polymorphisms and alter enzyme activity and concentration [31,32]. Thus, the benefit of investigating the relationship between the coding polymorphisms and CHD risk without considering confounding by promoter polymorphisms is limited.…”

Section: Pon55 Genotypementioning

confidence: 99%

Paraoxonase activity and coronary heart disease risk in healthy middle-aged males: The PRIME study

et al. 2008

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Objective: Classic coronary heart disease (CHD) risk factors fail to explain the large gradient in CHD incidence between Northern Ireland and France. The Prospective Epidemiological Study of Myocardial Infarction (PRIME) study, a multicentre prospective study of 10,593 middle-aged males, investigated novel risk factors in these populations. We tested the hypotheses that (1) higher paraoxonase activity is associated with decreased CHD risk and (2) PON55 LL genotype is associated with increased CHD risk. Methods: Paraoxonase activity was measured in 299 men who had developed CHD at 5-year follow-up and in 576 matched controls. DNA was available from 247 cases and 433 controls for genotyping for the PON55 polymorphism. Results: There was no significant difference in paraoxonase activity between cases and controls (geometric means 73.8 and 74.2 U/l; p = 0.81). There was no significant difference in CHD risk between fifths of paraoxonase activity either before (p = 0.55) or after adjustment for classical risk factors (p = 0.58).There was no significant association between genotype and CHD risk; relative to the LL genotype, the OR (95% CI) for the LM and MM genotypes were 0.92 (0.66-1.29) and 0.83 (0.50-1.36), respectively. The frequency of the L allele in cases (66.6%) and controls (64.5%) did not differ significantly, p = 0.45. Conclusions: These findings suggest that neither paraoxonase activity nor PON55 genotype is associated with CHD risk in males in the PRIME study.

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“…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]. However, the roles of these polymorphisms in atherosclerosis progression and in atherosclerosis therapy await experimental investigation.…”

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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Polymorphisms in the human paraoxonase (PON1) promoter

Cited by 170 publications

References 44 publications

Association Between p.Leu54Met Polymorphism at the Paraoxonase-1 Gene and Plantar Fascia Thickness in Young Subjects With Type 1 Diabetes

Association Between p.Leu54Met Polymorphism at the Paraoxonase-1 Gene and Plantar Fascia Thickness in Young Subjects With Type 1 Diabetes

Paraoxonase activity and coronary heart disease risk in healthy middle-aged males: The PRIME study

Effect of atorvastatin on paraoxonase1 (PON1) and oxidative status

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