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 ◽  
...  

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.

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Rakesh S Birjmohun ◽  
Menno Vergeer ◽  
Erik S Stroes ◽  
Michael W Tanck ◽  
Nicholas J Wareham ◽  
...  

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.


2016 ◽  
Vol 2016 ◽  
pp. 1-10
Author(s):  
Rafał Januszek

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.


1993 ◽  
Vol 39 (2) ◽  
pp. 209-212 ◽  
Author(s):  
J H Wu ◽  
J T Kao ◽  
M S Wen ◽  
D Wu

Abstract We measured lipid and lipoprotein concentrations in blood samples from control subjects and patients with coronary artery disease (CAD) in Taiwan. We found significant differences (P &lt; 0.01) in the concentrations of high-density lipoprotein cholesterol (HDLC), apolipoprotein AI (ApoAI), apolipoprotein B (ApoB), and lipoprotein(a) [Lp(a)]. Concentrations of HDLC &lt; 350 mg/L, ApoAI &lt; 900 mg/L, ApoB &gt; 800 mg/L, and Lp(a) &gt; 200 mg/L occurred, respectively, 2.8, 5.2, 1.7, and 2.3 times more frequently in the patients than in the control group. If one considers HDLC at &lt; 350 mg/L, ApoAI at &lt; 900 mg/L, ApoB at &gt; 800 mg/L, and Lp(a) at &gt; 200 mg/L as separate risk factors for CAD, the ratio of individual patients to control subjects having 4, 3, 2, 1, or 0 risk factors was [symbol: see text] 9.4, 2.1, 0.2, 0.2, respectively. Individuals displaying three or more risk factors were found 15 times more frequently in the CAD group than in the control group. These risk factors may be used clinically for the prediction and prevention of CAD in the general population.


2014 ◽  
Vol 04 (02) ◽  
pp. 094-097
Author(s):  
Deepti G. I. ◽  
Sukanya Shetty ◽  
Ashalatha V. Rao ◽  
Sarfraz Ahmad

Abstract: Background and objectives: Lipid disorder is a major risk factor for the progression of coronary artery disease. Age alone is a significant predictor of CVD risk in men and women. Before menopause, women have a much lower risk for cardiovascular events compared with men of their age. Reasons for protection from CVD in premenopausal women are complex, but a significant contribution can be assigned to the greater high-density lipoprotein (HDL) levels in younger women, which is an effect of estrogen. Methods: Fasting blood samples were collected from 40 healthy individuals (40 females divided into 2 groups according to age). Serum total cholesterol, triglycerides, and HDL- Cholesterol were estimated by enzymatic methods and LDL was calculated by Friedewald's equation. Results: The result showed increase in jyounger age group. Conclusion: It can be concluded that serum lipid profile changes can possibly be mediated by changing hormonal profile, especially estrogen which has role in lipid metabolism and indirectly on coronary artery disease.


2020 ◽  
Vol 21 (2) ◽  
pp. 88-96
Author(s):  
S.M. EL-Ageery ◽  
N.S. Gouda ◽  
I.M. Fawzy ◽  
A. Bahy-Eldeen ◽  
R. Mahmoud

Background: Studies have reported relationship between chronic  Helicobacter pylori infection and coronary artery disease (CAD). The  cytotoxin-associated gene A product (CagA) is an immunodominant protein which indicates infection with virulent H. pylori strains. Significant  associations of CagA-positive H. pylori strains with coronary artery disorders have been widely reported. H. pylori is also known to produce different heat shock proteins (HSPs) which can stimulate the production of specific  antibody against microbial proteins and capable of eliciting autoimmune reaction against human tissue expressing HSPs such as vascular  endothelial cells. The objectives of this study are to investigate the  association between H. pylori and CagA with coronary atherosclerosis and CAD, and to determine the possible role of H. pylori HSP60 protein in increasing the risk of CAD development. Methods: This study included 70 patients with stable angina and 70 age and gender-matched controls. Each group was evaluated by clinical history, physical examination, cardiac echocardiography (ECHO) and electrocardiography (ECG) with and without exercise. Fasting blood glucose, total cholesterol (TC), low density lipoprotein (LDL), high density lipoprotein (HDL) and triglycerides (TG) were estimated by automated enzymatic methods. H. pylori IgG, CagA IgG and HSP60 IgG were measured by enzyme-linked immunosorbent assay (ELISA) for both groups. Results: The seroprevalence of H. pylori infection was high in both groups; 75.7% in case and 68.6% in control (p=0.346). Serum IgG levels were significantly higher for CagA (p=0.028) and HSP60 (p<0.001) in cases than in controls. There was significant association between H. pylori and CagA IgGs in cases (p=0.007) but no association in controls (p=0.700). Higher HSP60 IgG level was significantly associated with both positive H. pylori IgG (p<0.001) and CagA IgG (p<0.001) in cases but no significant association was found with H. pylori (p=0.815) or CagA (p=0.332) IgG levels in the control group. Serum values were significantly higher for TC (p<0.001), TG (p<0.001) and LDL (p=0.004) while value for HDL was significantly lower (p<0.001) in H. pylori IgG-positive subjects (case and control). Conclusion: There is serological evidence that H. pylori infection may pose a significant risk factor for CAD. Since H. pylori can be eliminated by specific treatment, this may be a good preventive approach for CAD.Key words: H. pylori, coronary artery disease, CagA, HSP60, serology.


2005 ◽  
Vol 90 (4) ◽  
pp. 2264-2269 ◽  
Author(s):  
Marie-Claude Blatter Garin ◽  
Barbara Kalix ◽  
Alfredo Morabia ◽  
Richard W. James

Abstract The presence of the metabolic syndrome (World Health Organization definition) and its association with lipoprotein abnormalities suggestive of greater susceptibility to oxidative stress have been analyzed in patients with angiographically defined coronary artery disease. The odds ratio for the presence of the metabolic syndrome was significantly higher in coronary artery disease-positive patients (P &lt; 0.001). The metabolic syndrome was also associated with more severe coronary disease (P &lt; 0.01). Patients with the metabolic syndrome had significantly decreased low-density lipoprotein-cholesterol/apolipoprotein B and high-density lipoprotein-cholesterol/apolipoprotein AI ratios, indicative of the presence of small, dense lipoprotein particles. The syndrome was also associated with reduced concentrations and activities of the antioxidant enzyme, paraoxonase-1. The metabolic syndrome is characterized by smaller, denser lipoprotein particles that increase their susceptibility to oxidative modifications and diminished serum paraoxonase-1, which is a major determinant of the antioxidant capacity of high-density lipoproteins. These may be contributory factors to the increased presence and severity of coronary disease in such patients.


Author(s):  
Jelena Kotur-Stevuljevic ◽  
Slavica Spasic ◽  
Aleksandra Stefanovic ◽  
Aleksandra Zeljkovic ◽  
Natasa Bogavac-Stanojevic ◽  
...  

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


2013 ◽  
Vol 33 (suppl_1) ◽  
Author(s):  
Anandita P Agarwala ◽  
Jeffrey Billheimer ◽  
Amrith Rodrigues ◽  
Marjorie Risman ◽  
Marina Cuchel ◽  
...  

Plasma levels of high-density lipoprotein cholesterol (HDL-C) are strongly inversely associated with coronary artery disease (CAD) in epidemiologic studies, and high HDL-C is generally associated with apparent ‘protection’ from CAD. We have been recruiting individuals with high HDL-C for about 15 years, and while most have no CAD, a minority has premature CAD, a paradoxical phenotype. We hypothesize that such individuals may have HDL with altered structure and/ or function, and are systematically comparing these individuals (cases) to older individuals with extreme high HDL-C without CAD (controls) and a healthy control group with normal HDL-C levels. We identified 60 subjects with HDL-C above the 90th percentile, premature CAD, and no other major risk factors for coronary disease. We selected 2 controls per case, each matched for age, race, gender, and HDL level. Demographic information and lipid profile (mean ± SD) of the study groups are shown below. Controls are well matched to the cases. Studies are well underway to assess HDL size distribution by NMR, HDL composition, total and ABCA1-specific cholesterol efflux capacity, lecithin-cholesterol acyltransferase (LCAT) activity, and cholesteryl ester transfer protein (CETP) activity in cases and controls. We will also compare to a group of healthy controls with normal HDL-C levels. We expect that the findings from this study will provide insight into the etiology of CAD in this paradoxical phenotype.


2021 ◽  
Vol 8 (03) ◽  
pp. 136-140
Author(s):  
Rakhi Sasidharan Nair ◽  
Roshni Hareendra Babu ◽  
Shajee Sivasankaran Nair ◽  
Saboora Beegum

BACKGROUND Coronary artery disease is multifactorial in origin. Coronary artery disease predisposition is attributed to genetic factors also. Many gene polymorphisms are implicated out of which paraoxonase 1 (PON 1) gene is an important one. The product of paraoxonase gene is paraoxonase enzyme which is seen in serum associated with high density lipoprotein (HDL). This enzyme is mainly synthesised by the liver. The protective effect of HDL is attributed to the presence of such enzymes on it. Gln to Arg polymorphism at position 192 confers a risk of developing atherosclerosis and coronary artery disease (CAD). This study is done to assess the genotype distribution of PON 1 gene in CAD patients compared to healthy controls in a population from Kerala. METHODS The case group consists of 100 angiographically proven CAD patients with no history of hypertension, diabetes mellitus, hepatic disease or smoking. The control group had 100 healthy controls from the general population. PON 1 gene was amplified by a polymerase chain reaction (PCR) technique already reported and restriction fragment length polymorphism by the restriction enzyme Alwl was done to assess the polymorphism. to assess the polymorphism. RESULTS In this study, the frequency of heterozygous genotype QR was 86 % in control and 76 % in cases. Though there was no significant difference in allele distribution of Q or R, RR genotype was significantly higher in the case group ( 2 = 8.82; p value = .012). With binary logistic regression model, adjusting for age and sex, RR genotype is independently associated with CHD. Adjusted odds ratio of RR was 5.24 with 95 % confidence interval (CI) 1.41 - 19.47 for developing CHD (p < 0.05). CONCLUSIONS The RR genotype is more frequently seen in CAD patients than in controls. The QR genotype is more frequent than QQ or RR in both cases and controls. KEYWORDS Coronary Artery Disease, Paraoxonase, Gene Polymorphism


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