Abstract 3132: Paraoxonase-1 Activity Is not Independently Related with the Risk of Future Coronary Artery Disease

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Rakesh S Birjmohun ◽  
Menno Vergeer ◽  
Erik S Stroes ◽  
Michael W Tanck ◽  
Nicholas J Wareham ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Close Association ◽  
Conditional Logistic Regression ◽  
Hdl Cholesterol ◽  
Paraoxonase 1 ◽  
Pon1 Activity ◽  
Q192r Polymorphism ◽  
Artery Disease ◽  
Cad Risk

Background Paraoxonase-1 (PON1) is a potent antioxidant enzyme bound to high-density lipoprotein (HDL). Its activity, but not its concentration, is controlled by the PON1 Q192R polymorphism. PON1 is considered to protect against atherogenesis, but it is unclear whether this relation is independent of its carrier, HDL. Objective To evaluate the predictive value of PON1 for coronary artery disease (CAD) we assessed PON1 activity and genotype (Q192R polymorphism) in a large cohort. Methods and results We performed a case-control study nested in the prospective EPIC-Norfolk cohort. Cases (n = 1138) were apparently healthy men and women aged 45–79 years who developed fatal or nonfatal CAD during a mean follow-up of 6 years. Controls (n=2237) were matched by age and sex. Serum PON1 activity was lower in cases vs. controls (59.9 ± 44.6 U/L vs. 63.4 ± 46.7 U/L, p=0.020) and correlated with HDL cholesterol (r= 0.16, p<0.0001). Whereas the PON1 Q192R polymorphism strongly controlled PON1 activity (QQ: 27 ± 9, QR: 87 ± 27 and RR 152 ± 44 U/L), it was not related to the risk of future CAD (Odds Ratio [OR] per R allele 0.98 [0.84–1.15], p=0.84). Using conditional logistic regression, quartiles of PON1 activity showed a modest inverse relation with CAD risk (OR for the highest vs. the lowest quartile 0.77 [0.63– 0.95], p=0.013; p for trend over quartiles 0.064). PON1 activity adjusted for Q192R genotype - a proxy for PON1 concentration -correlated better with HDL cholesterol (r=0.29, p<0.0001) and strongly predicted CAD risk (OR for the highest versus the lowest quartile 0.72 (0.58 – 0.91), p for trend over quartiles = 0.005). However, this relation was abolished after adjustment for HDL related parameters (HDL particle number, HDL cholesterol, HDL size and apolipoprotein A-I; OR for highest vs. lowest quartile 0.87 [0.66 –1.16], p for trend over quartiles = 0.13). Conclusion In the largest prospective study to date, we show that PON1 activity inversely relates to CAD risk, but not independently of HDL, presumably due to its close association with the HDL particle. Since the Q192R polymorphism profoundly affects lifelong PON1 activity, our inability to demonstrate a relation between the Q192R polymorphism and CAD risk suggests that PON1 activity is not a causal factor in atherogenesis.

scholarly journals Reduced Paraoxonase 1 Activity as a Marker for Severe Coronary Artery Disease

2013 ◽  
Vol 35 ◽  
pp. 97-103 ◽  
Author(s):  
Chiyan Zhou ◽  
Jia Cao ◽  
Liang Shang ◽  
Chuanfeng Tong ◽  
Hanling Hu ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Atherosclerotic Lesion ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Paraoxonase 1 ◽  
Pon1 Activity ◽  
Control Group ◽  
Potential Biomarker ◽  
Artery Disease

Paraoxonase-1 (PON1), a high-density-lipoprotein- (HDL-) associated enzyme, has the potential to protect against atherogenesis. We examine the relationships between plasma PON1 activity and the progression of atherosclerosis as well as coronary artery disease (CAD). Fasting blood samples were collected from female apolipoprotein E-deficient (apoE−/−) mice and 149 patients undergoing coronary angiography for the biochemical parameters measurement. The severity of CAD was defined using angiographic Gensini score (GSS). Compared to 3-month-old apoE−/−mice, aged mice had significantly lower PON1 activity, which is negatively correlated with the size of atherosclerotic lesion and plasma interleukin-6 (IL-6) and tumor necrosis factorα(TNF-α) levels. In study patients, PON1 activity was correlated with age, sex, and HDL-cholesterol, apolipoprotein AI, and high-sensitivity C-reactive protein (hs-CRP) levels and was significantly lower in CAD group than that in non-CAD control group. Interestingly, PON1 activity in severe CAD group (GSS > 40) was further significantly reduced compared to those in mild and moderate subgroups (GSS  ≤ 40) (P<0.01). There is a significant correlation between PON1 activity and the severity of CAD as assessed by GSS (r=-0.393,P<0.001). PON1 activity may be a potential biomarker for the severity of CAD.

Paraoxonase-1 (PON1) activity, but not PON1Q192R phenotype, is a predictor of coronary artery disease in a middle-aged Serbian population

2006 ◽  
Vol 44 (10) ◽  
Author(s):  
Jelena Kotur-Stevuljevic ◽  
Slavica Spasic ◽  
Aleksandra Stefanovic ◽  
Aleksandra Zeljkovic ◽  
Natasa Bogavac-Stanojevic ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Paraoxonase 1 ◽  
Pon1 Activity ◽  
Middle Aged ◽  
Artery Disease

AbstractClin Chem Lab Med 2006;44:1206–13.

scholarly journals Paraoxonase-1 and Simvastatin Treatment in Patients with Stable Coronary Artery Disease

2016 ◽  
Vol 2016 ◽  
pp. 1-10
Author(s):  
Rafał Januszek
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Stable Coronary Artery Disease ◽  
Paraoxonase 1 ◽  
High Density Lipoproteins ◽  
Pon1 Activity ◽  
Control Group ◽  
Simvastatin Treatment ◽  
Simvastatin Therapy ◽  
Artery Disease

Background.Paraoxonase-1 (PON1) is the crucial antioxidant marker of high-density lipoproteins. The present study is aimed at assessing the effect of simvastatin treatment on PON1 activity and its relationship to Q192R and M55L polymorphisms in subjects with stable coronary artery disease (CAD).Methods.The patient group was composed of 53 individuals with stable CAD, and the control group included 53 sex-matched police officers without CAD. CAD patients were treated with simvastatin 40mg/day for 12 months. Respectively, flow mediated dilatation (FMD), serum hs-CRP and TNF-αlevels, urinary 8-iso-PGF2αconcentrations, and PON1 activity were evaluated in definitive intervals.Results.There was no effect of simvastatin treatment on urinary 8-iso-PGF2α. Simvastatin treatment significantly increased FMD value, decreased CRP and TNF-αconcentration. After adjusting for PON1 genotypes, significantly higher PON1 activity was noted in the 192R allele carriers, in both groups. Regardless of genotype, PON1 activity remained stable after simvastatin treatment.Conclusions.The present study confirms a positive effect of simvastatin therapy on endothelial function and inflammatory markers in secondary prevention. Simvastatin treatment shows no effects on PON1 activity and 8-isoprostanes level. The effect of simvastatin therapy on PON1 activity is not modulated by Q192R and M55L polymorphisms.

The Q192R polymorphism of the paraoxonase 1 gene is a risk factor for coronary artery disease in Saudi subjects

2013 ◽  
Vol 380 (1-2) ◽  
pp. 121-128 ◽  
Author(s):  
Mohammed A. Hassan ◽  
Omar S. Al-Attas ◽  
Tajamul Hussain ◽  
Nasser M. Al-Daghri ◽  
Majed S. Alokail ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Risk Factor ◽  
Coronary Artery ◽  
Paraoxonase 1 ◽  
Q192r Polymorphism ◽  
Artery Disease

scholarly journals Coronary artery disease risk in Chinese type 2 diabetics: is there a role for paraxonase 1 gene (Q192R) polymorphism?

2001 ◽  
pp. 639-644 ◽  
Author(s):  
D Osei-Hyiaman ◽  
L Hou ◽  
F Mengbai ◽  
R Zhiyin ◽  
Z Zhiming ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Central China ◽  
Paraoxonase 1 ◽  
Control Subjects ◽  
Q192r Polymorphism ◽  
Type 2 Diabetics ◽  
Artery Disease

OBJECTIVE: Heredity plays an important role in the predisposition to atherosclerotic coronary artery disease (CAD), and its thrombotic complications. Paraoxonase, a high-density lipoprotein-associated enzyme capable of hydrolyzing lipid peroxides, is presumed to contribute to atherosclerosis and CAD. This study investigates the role of human paraoxonase 1 (PON 1) gene (Q192R) polymorphism in CAD risk among Chinese type 2 diabetic cases. DESIGN: A population-based case-control study of paraoxonase 1 gene (Q192R) polymorphism and the risk of CAD in Chinese type 2 diabetics. METHODS: Subjects included 201 angiographically documented CAD patients with type 2 diabetes and 231 control subjects with type 2 diabetes alone living in central China. Single strand conformational polymorphism (SSCP) analysis was used to screen for PON 1 gene (Q192R) polymorphism. RESULTS: Frequency of the R allele was 21.5% in the CAD patients and 12.0% in the control subjects. The presence of the R allele was significantly associated with risk of CAD (odds ratio (OR)=1.97; 95% confidence interval (CI)=1.36--2.86). CONCLUSION: Frequency of the 192R allele of the human paraoxonase 1 gene may be an independent risk factor for CAD in the Chinese type 2 diabetics studied.

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