scholarly journals Genetic polymorphisms of paraoxonase 1 and susceptibility to atherogenesis

2013 ◽  
Vol 141 (9-10) ◽  
pp. 629-633 ◽  
Author(s):  
Ivana Grubisa ◽  
Petar Otasevic ◽  
Nada Dimkovic ◽  
Ivana Nedeljkovic ◽  
Bosko Toljic ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Clinical Manifestations ◽  
Density Lipoprotein ◽  
Rflp Analysis ◽  
Catalytic Efficiency ◽  
Paraoxonase 1 ◽  
Gene Variants ◽  
Pon1 Gene ◽  
Genotype Frequencies ◽  
Significant Difference

Introduction. Paraoxonase 1 (PON1) is a multifunctional enzyme associated with high-density lipoprotein particles (HDL). It is a cellular antioxidant that hydrolyses oxidized macromolecules, especially low-density lipoproteins (ox-LDL). Because increased oxidative stress is believed to play a crucial role in the initiation and propagation of atherosclerosis, coding (Q192R and L55M) and promoter (C(-107)T) region polymorphisms of pon1 gene, that are responsible for catalytic efficiency, activity and the level of the enzyme, have been of great interest as a potential markers of susceptibility for atherogenesis. Objective. The aim of the study was to assess possible association between these pon1 gene variants and clinical manifestations of the atherosclerosis and oxidative stress. Methods. A total of 60 angiographically documented patients with manifested atherosclerotic disease and 100 control individuals were analyzed. Genomic DNA was isolated from the peripheral blood cells and genotyping was performed using polymerase chain reaction followed by the restriction fragment length polymorphism (PCR-RFLP) analysis. Results No significant difference in allele and genotype frequencies of all three examined polymorphisms was found between the atherosclerotic patients and healthy controls. The obtained results could not support an association of pon1 gene variants with the oxidative stress and atherogenesis. Conclusion. These polymorphisms cannot be considered risk factors of atherosclerosis in Serbian population. A larger study is required in order to establish possible contribution of pon1 variants to atherosclerosis-related cardiovascular diseases.

Abstract 302: Presence of Oxidized Low-Density Lipoprotein in the Left Ventricular Blood of Subjects with Cardiovascular Diseases

2012 ◽  
Vol 32 (suppl_1) ◽  
Author(s):  
Chandrakala Aluganti Narasimhulu ◽  
Dmitry Litvinov ◽  
Danielle Jones ◽  
Chittoor Sai-Sudhakar ◽  
Michael Fristenberg ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Left Ventricular ◽  
Paraoxonase 1 ◽  
Left Ventricular Ejection ◽  
Low Density ◽  
Oxidized Low Density Lipoprotein ◽  
Peripheral Tissues ◽  
Significant Difference

Hypothesis: Oxidized low density lipoprotein (Ox-LDL) has properties that profoundly affect cardiovascular function. We hypothesized that Ox-LDL is likely to be formed in the left ventricular blood (LVB) when the heart is subjected to ischemic conditions and the ejection fraction (EF) is low. We speculated whether “stagnation” of LDL in the LV could result in increased formation of Ox-LDL. Objective: We studied whether there is an increased level of Ox-LDL in the LVB as opposed to peripheral blood (PB), and whether its presence correlated with the EF. Also we examined whether a higher level of Ox-LDL negatively correlated with the activity of paraoxonase 1 (PON 1). Methods: Following the Institutional Review Board (IRB) approval, 62 HF patients were enrolled in the study. All patients underwent pre-operative transthoracic echocardiographic assessment of ventricular function. Left ventricular ejection fractions were determined using the Simpsons bi-plane technique. 2ml of LVB and 5ml of PB samples were taken before coronary artery bypass surgery, or a surgery with replacement of mitral, aortic or tricuspid valve. Blood level of Ox-LDL was determined by ELISA (Mercodia), and PON 1 activity was determined by the rate of conversion of its substrate p-nitrophenyl acetate into p-nitrophenol. Results: The result showed significant increase in Ox-LDL in LVB as compared to PB (p=0.032) in HF subjects even when EF was near normal. There was no significant increase in subjects with lower EF. In contrast, Ox-LDL levels increased in the PB of subjects with lower EF and reached those of LVB. We also noticed that there was a statistically significant negative correlation between EF and Ox-LDL levels in both LVB and PB (p < 0.05). The activity of PON1, an antioxidant enzyme that protects LDL from oxidation showed decreased levels both in LV blood as well as in PB with decreased EF. It was observed that there was a statistically significant difference in PON1 levels between LV and PB of subjects having EF>60% (p = 0.03). Conclusions: In conclusion the results suggest that there might be oxidative stress associated with LVB even when the EF is not compromised. In contrast, the increase in PB Ox-LDL with poor EF might suggest that the low blood flow to peripheral tissues and end organs also might contribute to increased oxidative stress. The results also might suggest that persistent oxidative stress could have affected the clearance mechanisms of Ox-LDL.

Frequency of Human Paraoxonase-1 Q192R Polymorphism and Measurement of Oxidative Stress Parameters in Infants with G6PD Deficiency

2020 ◽  
Author(s):  
Vahid Pourshafiei ◽  
Vahide Jamshidi ◽  
Ameneh Khodarahmi ◽  
Mahmood Vakili
Keyword(s):  
Oxidative Stress ◽  
G6pd Deficiency ◽  
Paraoxonase 1 ◽  
Pon1 Activity ◽  
Stress Markers ◽  
Genotype Frequencies ◽  
Q192r Polymorphism ◽  
Significant Difference ◽  
And Control

Background and Aims: This study aimed to investigate the frequency of Q192R polymorphism and oxidative stress markers in infants with glucose-6phosphate dehydrogenase (G6PD) deficiency. Materials and Methods: This is a case-control study in which 60 male infants (2-4 months old) with G6PD deficiency along with 60 age- and sexmatched healthy neonates were included. The diagnosis of G6PD deficiency was made by Beutler test by which the G6PD enzyme activity is measured by the fluorescent spot test. The blood samples were taken from all infants, and the sera were isolated for the evaluation of Paraoxonase-1 (PON1) and malondialdehyde (MDA) using the spectrophotometric method. Restriction fragment length polymorphism was applied for determination of Q192R polymorphism (rs 662). Results: The frequencies of QQ, QR, and RR genotypes were 55%, 39%, and 6%, respectively in infants with G6PD deficiency while the above genotype frequencies were 45%, 49%, and 6%, respectively in healthy neonates. The frequency of R and T alleles failed to show any significant difference when G6PD deficient infants and healthy neonates were compared. The results indicated PON1 activity and MDA levels being significantly (p<0.05) higher in neonates with G6PD deficiency compared with their healthy counterparts. Conclusion: Contrary to previous studies, it was indicated that the presence of RQ and RR genotypes at Q192R position is associated with decreased activity of PON1 and increased oxidative stress. In this study, no significant differences were found in the genotype and allele frequency of PON1 Q192R polymorphism between the case and control groups. Also, this frequency was not consistent with the results obtained from oxidative stress conditions.

scholarly journals Association of Paraoxonase-1 Q192R (rs662) Single Nucleotide Variation with Cardiovascular Risk in Coffee Harvesters of Central Colombia

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Fernando Siller-López ◽  
Sandra Garzón-Castaño ◽  
Martha E. Ramos-Márquez ◽  
Iván Hernández-Cañaveral
Keyword(s):  
Cardiovascular Risk ◽  
Pesticide Exposure ◽  
Density Lipoprotein ◽  
Catalytic Efficiency ◽  
Paraoxonase 1 ◽  
Cvd Risk ◽  
Genotype Frequencies ◽  
Q192r Polymorphism ◽  
Ascvd Risk ◽  
Genetic And Environmental Factors

Paraoxonase 1 (PON1), a high-density lipoprotein-associated antioxidant enzyme, hydrolyzes several organophosphate pesticides and oxidized lipids. The PON1 Q192R polymorphism affects the catalytic efficiency and is considered a risk factor for pesticide intoxication and cardiovascular disease (CVD) but the association is not consistent between individuals or populations. We aimed to study the association of PON1 Q192R polymorphism with CVD risk in coffee harvesters of central Colombia. Demographics were collected from 205 subjects via standardized questionnaires. Lipid profiles and serum butyrylcholinesterase (BChE) were measured by standard procedures. The calculated 10-year atherosclerotic CVD (ASCVD) risk was used as the cardiovascular risk estimate. Q192R genotype was determined by real-time PCR. Prevalence of hypertension, hypercholesterolemia, and the 10-year ASCVD risk was 33%, 62%, and 22%, respectively. BChE levels were no indicative of recent pesticide exposure, although a positive correlation was observed with BChE and hypercholesterolemia. The Q192R genotype frequencies were 38% (QQ), 44% (QR), and 18% (RR). We found an association of the 192Q genotype with hypertension. The results of this study signal the importance to evaluate the influence and potential interactions of BChE and PON1 192Q allele with known genetic and environmental factors implicated in the pathogenesis of CVD.

scholarly journals The association between PON1 gene polymorphisms (Q192R and L55M) and nephrotic syndrome in Iraqi children

2021 ◽  
Vol 2 (03) ◽  
pp. 118-130
Author(s):  
Raghad Ali ◽  
Rayah Baban ◽  
Shatha Ali
Keyword(s):  
Nephrotic Syndrome ◽  
Lipid Profile ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Paraoxonase 1 ◽  
Pon1 Activity ◽  
Healthy Controls ◽  
Coding Region ◽  
Pon1 Gene ◽  
Homozygous Genotype

Background: The role of paraoxonase 1 enzyme (PON1) and its single nucleotide polymorphisms (SNPs) in children with nephrotic syndrome (NS) has been reported previously in different ethnic and racial groups with divergent results. The human PON1 gene contains two coding region polymorphisms leading to two different PON1 isoforms. Objectives: The aim of the present study was to find out the association between the PON1 (Q192R and L55M) polymorphisms and their relation with serum PON1 activity as well as lipid profile tests (total cholesterol, TC; triglycerides, TG; high-density lipoprotein cholesterol, HDL-c; and low-density lipoprotein cholesterol, LDL-c) in children with NS. Methods: This study included a total of 80 participants (40 with NS in the age group of 2-14 years and 40 age and sex-matched healthy controls). The PON1 enzyme activity and lipid profile tests were measured in serum samples of all included participants. The PON1 genotype was determined by PCR-restriction enzyme fragment length polymorphism (PCR-RFLP) for both PON1 alleles (192 and 55) SNPs. Results: Our findings showed that the mean levels of lipid profile tests (TC, TG, LDL-c) were significantly increased in patients when compared with healthy controls (p<0.05), while the HDL-c concentration was significantly decreased in patients than that of controls. Also, the patients had significantly lower concentrations of PON1 when compared with the controls regardless of the genotype Q192R and L55M polymorphisms. Moreover, the homozygous RR genotype for PON1 SNP 192 and MM homozygous genotype for PON1 SNP 55 were significantly frequent in patients when compared with the controls. Conclusions: Our results support that the presence of the homozygous RR genotype for PON1 SNP 192 and MM homozygous genotype for PON1 SNP 55 were significantly higher in patients compared with the controls.

scholarly journals Paraoxonase 1 (PON1) Gene Variants Are Not Associated With Clopidogrel Response

2011 ◽  
Vol 90 (4) ◽  
pp. 568-574 ◽  
Author(s):  
J P Lewis ◽  
A S Fisch ◽  
K Ryan ◽  
J R O'Connell ◽  
Q Gibson ◽  
...  
Keyword(s):  
Paraoxonase 1 ◽  
Gene Variants ◽  
Pon1 Gene

scholarly journals Plasma Markers of Oxidative Stress in Patients with Gestational Diabetes Mellitus in the Second and Third Trimester

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Hongwei Li ◽  
Qian Yin ◽  
Ning Li ◽  
Zhenbo Ouyang ◽  
Mei Zhong
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Pregnant Women ◽  
Paraoxonase 1 ◽  
Third Trimester ◽  
Significant Difference ◽  
Markers Of Oxidative Stress ◽  
Plasma Markers

Objective.To determine plasma markers of oxidative stress during the second and third trimester of pregnancy in patients with gestational diabetes mellitus (GDM).Study Design.We conducted a prospective nested case-control study involving 400 pregnant women, 22 of whom developed GDM. As control group, 30 normal pregnant women were chosen randomly. Plasma samples were analyzed for 8-iso-prostaglandin F2α(8-iso-PGF2α), advanced oxidative protein products (AOPPs), protein carbonyl (PCO), glutathione peroxidase-3 (GPX-3), and paraoxonase-1 (PON1) at 16–20 weeks, 24–28 weeks, and 32–36 weeks of gestation.Results.Compared to control subjects, the plasma levels of PCO, AOPPs, and 8-iso-PGF2αwere elevated at 16–20 weeks’ and 32–36 weeks’ gestation in GDM. There was no significant difference in PCO and 8-iso-PGF2αat 24–28 weeks in GDM. GPX-3 was statistically significantly increased at 16–20 weeks and 32–36 weeks in GDM. PON1 reduced in patients with GDM. No significant differences were found at 24–28 and 32–36 weeks between the GDM and control groups. In GDM, PCO, AOPPs, and 8-iso-PGF2αlevels were higher and GPX-3 and PON1 levels were lower in the second than the third trimester.Conclusion.Oxidation status increased in GDM, especially protein oxidation, which may contribute to the pathogenesis of GDM.

scholarly journals Role of CYP2E1 and NQO1 polymorphisms in oxidative stress derived cancer in Thais with and without dyslipidemia

2017 ◽  
Vol 9 (5) ◽  
pp. 601-611
Author(s):  
Pharrunrat Tanaviyutpakdee ◽  
Krongtong Yoovathaworn ◽  
Jintana Sirivarasai ◽  
Suwannee Chanprasertyothin ◽  
Pachara Panpunuan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Density Lipoprotein ◽  
Blood Lipid ◽  
Lipoprotein Cholesterol ◽  
Blood Cholesterol ◽  
Genotype Distribution ◽  
Related Factors ◽  
Genotype Frequencies ◽  
Oxidative Stress Status ◽  
Variant Alleles

Abstract Background Hyperlipidemia can induce the endogenous production of reactive oxygen species (ROS), which may cause carcinogenesis. Cytochrome P450 (CYP) 2E1 activity, induced by various factors including polyunsaturated fatty acids, effects the incidence of cancers, whereas NQO1, a flavoprotein, may protect against ROS. Objectives To investigate the effect of CYP2E1 and NQO1 polymorphism on oxidative stress status in Thais with and without dyslipidemia. Methods We included 1380 apparently healthy employees of the Electricity Generating Authority of Thailand in this study. We determined their CYP2E1 and NQO1 genotypes and related these to blood lipid profiles, and circulating levels of antioxidant enzymes, malondialdehyde (MDA), and reduced glutathione (GSH). Lifestyle-related factors were determined from questionnaires. Results All tested genotype frequencies were in Hardy-Weinberg equilibrium. The heterozygous and variant genotype distribution and allele frequency of CYP2E1 *5B were less common than CYP2E1 *6. Heterozygous NQO1 was the most prevalent form. The frequency of the mutated allele CYP2E1 *5B was 0.16, CYP2E1 *6 was 0.22, and NQO1 *2 was 0.43. Significant differences were observed for blood cholesterol, triglyceride, low-density lipoprotein-cholesterol, and high-density lipoprotein-cholesterol between normolipidemic participants, and those with hypercholesterolemia, hypertriglyceridemia, and combined hyperlipidemia. Participants in the hyperlipidemic subgroup who bore any variant alleles of genes had higher plasma MDA and GSH levels, and superoxide dismutase and glutathione peroxidase activity, but lower catalase activity when compared with normolipidemic participants bearing wild-type alleles. Conclusions Variations in genetic disposition and dyslipidemia can modify oxidative stress status. Relatively more free radicals may be generated in individuals in subgroups with hyperlipidemia bearing any variant alleles.

scholarly journals New Markers of Platelet Activation and Reactivity and Oxidative Stress Parameters in Patients Undergoing Coronary Artery Bypass Grafting

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Petar Vukicevic ◽  
Aleksandra Klisic ◽  
Vojislava Neskovic ◽  
Luka Babic ◽  
Aleksandar Mikic ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Coronary Artery ◽  
Coronary Artery Bypass ◽  
Platelet Activation ◽  
Artery Bypass ◽  
Paraoxonase 1 ◽  
Syntax Score ◽  
Lipid Hydroperoxides ◽  
Distribution Width ◽  
Significant Difference

Objective. Recent studies have shown that the red cell distribution width- (RDW-) to-platelet (PLT) count ratio (i.e., RPR) and the mean platelet volume (MPV)/PLT ratio (i.e. MPR) are more sensitive markers of atherosclerosis-connected risk than RDW and PLT alone. The present study is aimed at investigating the oxidative stress status and these two new markers of platelet activation in two different heart surgery modalities: cardiopulmonary bypass (CPB) and off-pump coronary artery bypass (OPCAB). We also aimed to test the possible relationship between RPR and MPR, respectively, and the severity and complexity of atherosclerotic plaque, measured as Syntax Score. Patients and Methods. A total of 107 patients encompassed this prospective study (i.e., 60 patients in CPB group and 47 patients in OPCAB). Blood samples were drawn at several time intervals: before skin incision (t1), immediately after intervention (t2), 6 h (t3), 24 h (t4), 48 h (t5), and 96 h after cessation of the operation (t6). Results. The values of RPR and MPR were similar in CPB and OPCAB before surgery and started to rise in t2 (i.e., immediately after the intervention). This increase lasted to t5 (i.e., 48 hours after the intervention), when it became the highest. After that, both markers started to regress about the 96th hour after the beginning of surgery. Nominal values of both indices were higher in CPB than in OPCAB in all study points after the surgery. Furthermore, a significantly higher level of antioxidative parameters (i.e., total sulfhydryl groups and paraoxonase 1) in the OPCAB group compared to the CPB group was noted at t5 study point (i.e., 48 hours after the surgery), whereas no significant difference was noted in prooxidant levels (i.e., lipid hydroperoxides and advanced oxidation protein products) between these groups at this study point. MPR and RPR correlated positively with Syntax Score at several study points after the surgery completion. Syntax Score, MPR, and RPR showed good clinical accuracy in surgery-related complication prediction (( AUC = 0.736 ), 95th CI (0.616-0.856), P = 0.003 )). Conclusion. When combined, MPV, RDW, and platelet count, such as MPR and RPR, could be good predictors of coronary artery disease status, regarding the aspect of joint inflammation, oxidative stress, and thrombosis.

scholarly journals Association of Leptin Gene Polymorphisms with Rheumatoid Arthritis in a Chinese Population

2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Sha-Sha Tao ◽  
Yi-Lin Dan ◽  
Guo-Cui Wu ◽  
Qin Zhang ◽  
Tian-Ping Zhang ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Chinese Population ◽  
Clinical Manifestations ◽  
Enzyme Linked Immunosorbent Assay ◽  
Healthy Controls ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Genotype Frequencies ◽  
Significant Difference ◽  
Plasma Leptin

Background. Recently, increasing studies have revealed that leptin is involved in the development of rheumatoid arthritis (RA). This study is aimed at exploring the association of leptin gene single nucleotide polymorphisms (SNPs) with susceptibility to RA in a Chinese population. Methods. We recruited 600 RA patients and 600 healthy controls from a Chinese population and analyzed their three leptin SNPs (rs10244329, rs2071045, and rs2167270) using the improved Multiplex Ligase Detection Reaction (iMLDR) assays. The associations of these SNPs with clinical manifestations of RA were also analyzed. Enzyme-linked immunosorbent assay (ELISA) was performed for plasma leptin determination. Results. No significant difference in either allele or genotype frequencies of these three SNPs between RA patients and healthy controls was observed (all P > 0.05 ). Association between the genotype effects of dominant, recessive models was also not found (all P > 0.05 ). No significant difference in plasma leptin levels was detected between RA patients and controls ( P > 0.05 ). Conclusion. Leptin gene (rs10244329, rs2071045, and rs2167270) polymorphisms are not associated with RA genetic susceptibility and its clinical features in the Chinese population.

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