Paraoxonase 1 Arylesterase Activity Research Articles

Role of Myeloperoxidase, Paraoxonase, and Nitric Oxide System in the Blood and Pericardial Fluid of Patients with Ischemic Heart Disease after Direct Myocardial Revascularization

To study the role of paraoxonase, myeloperoxidase, arginase, asymmetric dimethylarginine, and nitric oxide in the mechanisms of the pathogenesis of postpericardiotomy syndrome (PPCS), 76 patients with ischemic heart disease (IHD) who underwent coronary artery bypass grafting were examined. Patients were divided into two groups: Group 1, IHD patients who were not diagnosed with PPCS as a result of clinical studies, and Group 2, IHD patients who were diagnosed with PPCS. The results indicate that the postoperative period after coronary artery bypass grafting is associated with the inhibition of paraoxonase, the activation of myeloperoxidase, enhanced arginase activity, increased nitrite/nitrate and asymmetric dimethylarginine levels; it may also be accompanied by the development of endothelial dysfunction and increased systemic inflammatory response. In the present work, inverse correlations were found between the paraoxonase aryl esterase activity and myeloperoxidase activity in plasma, as well as the paraoxonase aryl esterase activity in blood plasma and arginase activity in erythrocytes in patients of both groups. Tests to predict the development of postpericardiotomy syndrome were developed based on the ratio of activity of the studied enzymes.

Crosstalk Between Adipokines and Paraoxonase 1: A New Potential Axis Linking Oxidative Stress and Inflammation.

Paraoxonase 1 (PON1) is a high-density lipoprotein (HDL)-associated protein that endows its carrier with (lipo-)lactonase-dependent antioxidative features. Low levels of PON1 activity have been observed in association with obesity, a major risk factor for cardiovascular disease (CVD). Considering the well-recognized atheroprotective role of PON1, exogenous/endogenous factors that might modulate its levels/activity are raising great interest. Since adipokines represent a molecular link between obesity and CVD, we here explored the possible impact of these substances on PON1 activity/expression. The levels of interleukin (IL)-6, IL-8, tumor necrosis factor alpha, monocyte chemoattractant protein-1, hepatocyte growth factor, resistin, leptin, and adiponectin were measured along with arylesterase, paraoxonase, and lactonase activities of PON1 in 107 postmenopausal women. Moreover, the direct effect of resistin on PON1 expression was evaluated in vitro. Multivariate analysis revealed that only resistin was significantly and inversely correlated with PON1-lactonase activities (r = −0.346, p < 0.001) regardless of confounding factors such as age or HDL-cholesterol. It is worth noting that no statistical link was found between adipokine and arylesterase or paraoxonase, the two promiscuous activities of PON1. Notably, resistin down-regulated PON1 expression occurred in hepatocellular carcinoma cultures. Our study suggests that resistin might be a negative modulator of PON1 expression and anti-oxidative activity.

PON1 arylesterase activity, HDL functionality and their correlation in malnourished children.

Background The study was done to assess high-density lipoprotein (HDL) functionality and to correlate this with paraoxonase 1 (PON1) activity in malnourished children. It aimed to find the effect of malnutrition on changes in PON1 activity, HDL functionality, lipid profile and lipid hydroperoxide formation. Methods This case control study included 30 malnourished children (up to age 5 years) and 30 healthy controls in the paediatric inpatient department of SRTR Government Medical College Ambajogai, India. Clinically diagnosed cases depending on anthropometric indices were selected. Serum PON1 activity by using phenyl acetate as a substrate, HDL functionality by haemin by its protection on H2O2 and haemin induced LDL oxidation, lipid profile by routine enzymatic methods and lipid hydroperoxide using the FOX2 assay were measured. Results Malnourished children had significantly decreased PON1 activity (106.6 ± 12.74** vs. 132.23 ± 28.49 IU/L), HDL functionality (116.55 ± 8** vs. 132.29 ± 10.9%), total cholesterol (TC) (102.5 ± 16** vs. 116.4 ± 12.65 mg/dL), HDL-cholesterol (C) (33.41 ± 9.74** vs. 40.55 ± 5.85 mg/dL) and reduced total protein level (5.56 ± 0.91* vs. 6.06 ± 1.055) higher triglycerides (TG) (146.76 ± 34.97* vs. 125.96 ± 17.21 mg/dL) level and total hydroperoxide (TPX) levels (5.568 ± 1.70** vs. 3.22 ± 1.52 μM/L). *p < 0.05 **p < 0.001. PON1 activity (r2 = 0.576) and TC (r2 = 0.567) shows significant positive correlation with HDL functionality. PON1 activity, HDL-C, HDL functionality and TPX shows independent contribution towards malnutrition in children in multivariate and univariate logistic regression. TC lost its significance in multivariate regression. Conclusions Malnutrition leads to decrease in HDL functionality and increase in hydroperoxide levels with a decrease in PON1 activity.

Organochlorine and organophosphorus pesticides and bladder cancer: A case-control study.

Exposure to pesticides is associated with an increase in the incidence of cancer. We aimed to investigate the association of serum organochlorine pesticides (OCPs) and organophosphorus pesticides (OPs) levels and GSTM1/GSTT1 gene polymorphism with bladder cancer (BC). This study was performed on 57 patients with BC and 30 controls (C). Acetylcholinesterase (AChE) activity, arylesterase activity of paraoxonase-1 (ARE), total antioxidant capacity (TAC), and malondialdehyde (MDA) levels were determined in serums of all participants. Genomic DNA was extracted using the salting out method and GSTM1/GSTT1 gene polymorphisms were examined by multiplex polymerase chain reaction assay. Measurement of OCPs (α-hexachlorocyclohexane [α-HCH], β-HCH, γ-HCH, 2,4-dichlorodiphenyltrichloroethane [2,4-DDT], 4,4-DDT, 2,4- dichlorodiphenyldichloroethylene [2,4-DDE], and 4,4-DDE) in serum was carried out using an FID-equipped gas-chromatography system. AChE activity was significantly lower, ARE activityand TAC were declined but it was not statistically significant, however, α-HCH, γ-HCH, 4,4-DDE, 2,4-DDT, and 4,4-DDT pesticides, and MDA were significantly higher in BC patients compared with the control subjects. Also, a positive correlation was found between the number of smoked cigarettes and the years of smoking with BC development. There was no association between GSTM1/GSTT1 gene polymorphisms and OCPs in BC patients. Due to the higher levels of some OCPs in the BC patients, along with the reduction in AChE activity and increased MDA levels, it may be concluded that OCPs and OPs play an important role in the induction of BC in southeastern Iran.

Influence of nutritional factors and the PON1 C(-107)T polymorphism on paraoxonase-1 activity in childhood

ObjectiveThe cardioprotective enzyme paraoxonase-1 (PON1) suffers an important influence from genetic polymorphisms and nutritional factors. The aim of this study was to investigate the influence of diet, nutritional status, and the C(-107)T polymorphism on PON1 arylesterase activity in children. MethodsThis was a cross-sectional study with 97 children, aged between 5 and 8 years, of both genders, from a pediatric outpatient clinic in southern Brazil. A sociodemographic, behavioral, and food consumption questionnaire was applied, and anthropometric measurements and laboratory blood samples were taken. PON1 arylesterase activity was measured by phenol extinction (U/mL), and DNA extraction and analysis of the PON1 C(-107)T polymorphism were performed. The Hardy–Weinberg equilibrium was tested with the chi-squared test and linear regression was used to estimate PON1 activity according to four adjustment models, with an acceptable error of 5%. ResultsIn the sample, the male gender accounted for 50.5%, 39.2% were 6 years of age, 54.5% had normal weight, and 51.5% had PON1 activity below the median (90.0, 15–30U/mL). Genotype frequency was 54.6% (53/97), 31.0% (30/97), and 14.4% (14/97), respectively, for CT, CC, and TT, consistent with the Hardy–Weinberg equilibrium (p=0.22). In the regression analysis, the model that included sociodemographic variables as well as frequency of consumption of fruits, vegetables, legumes, dairy products, and beans estimated a variability of 14.8% in PON1 activity combined with the PON1 C(-107)T polymorphism. ConclusionsDuring childhood, a good-quality diet with greater inclusion of healthy foods was important to predict the activity of the cardioprotective enzyme PON1 combined with the C(-107)T polymorphism of the PON1 gene.

Organochlorine and organophosphorous pesticides may induce colorectal cancer; A case-control study

ObjectivesAmong the numerous agents, genetic factors and environmental elements such as pesticides have an important role in colorectal cancer (CRC) incidence. The present study aimed to investigate the probable-role of some organochlorine pesticides (OCPs) and organophosphorous pesticides (OPPs) in patients with CRC. MethodsIn this case-control study, 42 patients with CRC and 30 healthy subjects were selected. The serum levels of some OCPs (α-HCH, β-HCH, γ-HCH, 2,4 DDE, 4,4 DDE, 2,4DDT and 4,4DDT) were measured by gas chromatography (GC) method. Serum levels of malondialdehyde (MDA), and total antioxidant capacity (TAC) as well as the enzyme activity of acetylcholinesterase (AChE) and arylesterase activity of Paraoxonase-1 (PON-1) were evaluated in all participants. The methylation specific PCR (MSP) assay was used for determining the methylation status of CpG island of p16 and MGMT genes in CRC patients. ResultsThe mean serum levels of each OCPs were significantly higher in the patient group compared to the control group (P < 0.001). The AChE and arylesterase activity of PON-1 in the patient group were significantly lower than the control group (P < 0.001). The mean serum levels of MDA and TAC in the serum of the patient group were significantly higher than the control group (P < 0.001 and P < 0.002, respectively). The current findings demonstrated significantly hypermethylation of p16 promoter in CRC patients. ConclusionRegarding the higher levels of OCPs in CRC patients, along with hypermethylation of the p16 promoter gene, diminishing in AChE and PON-1 activity and increasing in oxidative stress factors, the role of OCPs and OPPs in the CRC progression in the South-East of Iran may be assumed.

Relationship of High-Density Lipoprotein-Associated Arylesterase Activity to Systolic Heart Failure in Patients with and without Type 2 Diabetes

High-density lipoprotein (HDL) confers protection against cardiovascular disease partly attributable to its robust anti-oxidant activities, which is largely impaired in diabetic conditions. In this study, we analyzed the anti-oxidant activity of HDL, as represented by the arylesterase activity of paraoxonase 1 (PON1) in HDL particles, in 216 consecutive HF patients with (n = 79) or without (n = 137) type 2 diabetes, and age- and gender-matched 112 diabetic and 189 non-diabetic non-HF controls. We found arylesterase activity was significantly decreased in patients with than without HF, and was further decreased when comorbid with diabetes. After adjusting for conventional risk factors and apolipoprotein A-I levels, arylesterase activity remained correlated positively with left ventricular ejection fraction in diabetic (r = 0.325, P = 0.020) but not non-diabetic patients (r = 0.089, P = 0.415), and negatively with NT-proBNP and NYHA functional class in both subgroups. In regression analyses, a higher risk of HF was observed in diabetic than non-diabetic patients when having low arylesterase activities. In conclusion, our data demonstrate that impaired serum arylesterase activity in patients with HF is further reduced when comorbid with diabetes. The relationship of impaired arylesterase activity to HF is especially enhanced in diabetic patients.

Evaluation of Relationship Between Arylesterase-Based Activity and Genetic Variants of Paraoxonase1 in T2DM Patients within Golestan Province.

Arylesterase activity of Paraoxonase-1 (PON1) enzyme may be play important role in initiation and progression of several diseases. Activity or serum level of Arylesterase can be affected by many genetic alterations such as SNPs. The reduction in the activity and serum level of Arylesterase could be involved in Type2 diabetes mellitus (T2DM). The aim of this investigation is to examine the association between Arylesterase activity and promoter polymorphism (- 108C > T) of PON1gene in patients with T2DM in Golestan Province, northern area of Iran. Achievement of this purpose was due to DNA obtaining from blood then SNP determination using PCR-RFLP and Arylesterase activity measurement in the serum of 90 normal individuals and 90patients suffering diabetes. Data was processed by SPSS software version 16. The significant association was observed between the Arylesterase activity and three genotypes of PON1 gene such as CC, CT, and TT in subjects with T2DM. In the present study, it has been shown level of Arylestrase activity of PON1 in patients (117.33 ± 63.96) is lower than it in control group (289.33 ± 68.38); P < 0.05. Our results declared that activity of Arylesterase in diabetic patients was significantly lower than the healthy individuals.

Cardiovascular Insufficiency, Abdominal Sepsis, and Patients' Age Are Associated with Decreased Paraoxonase-1 (PON1) Activity in Critically Ill Patients with Multiple Organ Dysfunction Syndrome (MODS).

Oxidative stress and uncontrolled inflammation are hallmarks of sepsis, leading to organ failure and death. As demonstrated in animal studies, oxidative stress can be alleviated by antioxidant therapies. Paraoxonase-1 (PON1) is a serum-based antioxidant, anti-inflammatory agent, detoxifier, and quorum-sensing factor found to be a prognostic marker in sepsis. However, its associations with multiple organ dysfunction syndrome (MODS), a complication of sepsis and the leading cause of death in the surgical intensive care units (ICU), as well as with specific organ dysfunction, infection site, and invading pathogen remain unknown. Therefore, we measured arylesterase activity of PON1 in 87 individuals (35 with MODS) and related it to the clinical type, organ failure, infection site, pathogens, and hematological and biochemical indices of inflammation at admission to ICU and during a five-day follow-up. Suitability of PON1 and its indices derived from a follow-up as biomarkers in MODS was evaluated as well. MODS was associated with decreased PON1, more so in patients with septic shock, displaying an excellent accuracy as a marker of MODS (91%) and a fair one as a marker in differentiating septic shock from severe sepsis (76%). Decreased admission PON1 accompanied cardiovascular insufficiency (CVI), and, as its marker, PON1 displayed a good accuracy (82%). It was also associated with the abdomen as a site of infection but not with an invading pathogen. In multivariate analysis, 50% of variability in PON1 activity in patients with MODS was explained by the patients' age, CVI, and abdomen as a site of infection. Patients with septic shock, CVI, and abdominal MODS had distinctly different dynamics of PON1 during a follow-up. Mean PON1 activity during the follow-up reflected the associations observed for admission PON1 but was also significantly associated with metabolic dysfunction. Our results show PON1 potential as a biomarker in MODS, particularly as an indicator of CVI.

Sex difference: an important issue to consider in epidemiological and clinical studies dealing with serum paraoxonase-1.

The aim of this study was to evaluate the influence of sex on serum paraoxonase-1 (PON1) activities and on its relationship with cardiovascular disease risk factors such as overall and central obesity. Arylesterase and lactonase activities of PON1 were assessed in 374 women and 92 men. Both arylesterase and lactonase activities were significantly higher in women compared to men (p<0.001), irrespectively of confounders such as high density lipoprotein-cholesterol, age, smoking and body mass index or waist circumference. Sex also strongly influenced the interplay between PON1 and both fat measures, with only the arylesterase showing a significant and independent inverse correlation with the former parameter (r = −0.248, p<0.001) and the risk of overall obesity (odds ratio: 0.559, 95% confidence interval: 0.340–0.919) in women, but not in men; conversely, neither of the two activities remained associated with waist circumference in men or women after full adjustment. Noteworthy, the association between arylesterase and BMI in the female subsample was significant among women younger than forty-five years (r = −0.453, p<0.001, R2 = 0.207). In conclusion, our study suggests that sex might chiefly influence PON1 activity and its contribution to cardiovascular disease risk. Further studies are needed to confirm and clarify our preliminary findings.

Correlation Between Serum PON1 Arylesterase Activity and Rs 854573 &amp;lt;i&amp;gt;PON1 A &amp;lt; G&amp;lt;/i&amp;gt; Polymorphism with Type 2 Diabetes in an Eastern Indian Cohort

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder of glucose and lipids and characterized by defect in insulin secretion or action. Oxidative imbalance has also been implicated in the etiology of diabetes. Paraoxonase-1 (PON1) is an esterase and lactonase which is found in the circulation bound to high-density lipoproteins (HDL). Alterations and associations of circulating PON1 levels with a variety of diseases including diabetes encourages us to investigate the possible association between PON1 A/G rs854573 polymorphism and serum PON1 activity with T2DM. The study essentially follows a population based case-control format with 101 diabetic and 102 healthy controls. The findings revealed association of polymorphism with the diseased status (p value 0.0002, OR 3.49, 95% CI 1.77 to 6.9). With significantly higher range of mean serum PON1 Arylesterase (AREase) activity in control (9.99 – 0.96 kU/L) than in diabetic patients (5.25 - 0.508 kU/L) (p value,<0.001), a large difference between common diabetic AA genotype and combined diabetic heterozygous and homozygous genotypes (AG+GG) for risk allele G (assymptometic p value,<0.001), or in between two AA genotypes (Diabetic/Non diabetic, p<0.001), was explored by parametric and non parametric statistical pairwise comparison. Serum PON1 activity was found to be independent of other clinical factors such as plasma glucose levels. Western blot analysis of serum samples detected a significant difference of PON1 proteins in diabetic patients and control subjects (p value 0.008). In conclusion serum PON1 AREase activity which to an extent correlated with PON1 promoter polymorphism might be a good predictor of the disease risk.

Erratum: Decreased serum PON1 arylesterase activity in familial hypercholesterolemia patients with a mutated LDLR gene

[This corrects the article doi: 10.1590/1678-4685-gmb-2016-0287].

Changes in lecithin: cholesterol acyltransferase, cholesteryl ester transfer protein and paraoxonase-1 activities in patients with colorectal cancer

BackgroundPrevious studies revealed decreased level of high-density lipoprotein cholesterol (HDLC) as important factor for development of colorectal cancer (CRC). Quantity and structure of HDL particles depend on activities of lipid transfer proteins lecithin:cholesterol acyltransferase (LCAT) and cholesteryl ester transfer protein (CETP), but this topic is largely unexplored in CRC. The main objective of this study was to investigate activities of LCAT and CETP in patients with CRC. Additionally, we analyzed activity of paraoxonase-1 (PON-1), as a main carrier of HDL-antioxidant function. Materials and methodsNinety-nine CRC patients and 101 healthy individuals were included. LCAT and CETP activities were assessed by measuring rates of formation and transfer of cholesteryl esters. PON-1 paraoxonase and arylesterase activities were measured. ResultsLower levels of HDL-C (p < .001) were observed in cohort of patients, alongside with decreased LCAT (p < .050) and increased CETP activity (p < .050). Both PON-1 activities were diminished in CRC (p < .050 and p < .001 respectively). Univariate logistic regression singled out HDL-C level (OR = 0.218, p < .001), CETP activity (OR = 1.010, p < .01) and mass (OR = 0.994, p < .001) as possible markers of elevated CRC risk. CETP mass maintained its predictive significance when adjusted for traditional risk factors and level of oxidative stress (OR = 0.993, p < .001; OR = 0.982, p < .050, respectively). ConclusionOur results demonstrated increased CETP and decreased LCAT and PON-1 activities in CRC patients. In preliminary analysis CETP mass was identified as potential significant predictor of CRC development, suggesting that alterations in HDL-C levels, alongside with changes in HDL structure might have a role in carcinogenesis.

Long-Term Supplementation of Black Elderberries Promotes Hyperlipidemia, but Reduces Liver Inflammation and Improves HDL Function and Atherosclerotic Plaque Stability in Apolipoprotein E-Knockout Mice.

HDL particles are protective against atherosclerosis, but may become dysfunctional during inflammation and chronic disease progression. Anthocyanin-rich foods, such as the black elderberry, may improve HDL function and prevent disease development via antioxidant and/or anti-inflammatory effects. This study investigates the long-term consumption of black elderberry extract (BEE) on HDL function and atherosclerosis in apolipoprotein (apo) E-/- mice. ApoE-/- mice (n = 12/group) are fed a low-fat diet, supplemented with 0, 0.25%, or 1% (by weight) BEE (≈37.5-150 mg anthocyanins per kg body weight) for 24 weeks. Feeding 1% BEE increases total serum cholesterol (+31%) and non-HDL cholesterol (+32%) compared with the control diet. PON1 arylesterase (+32%) and lactonase (+45%) activities also increase with the 1% BEE diet. Both 0.25% BEE and 1% BEE diets strongly increase HDL cholesterol efflux capacity (CEC) by 64% and 85%, respectively. Further, BEE dose-dependently lowers serum liver enzymes and hepatic inflammatory gene expression. Although there is no change in neutral lipid accumulation in atherosclerotic lesions, BEE promotes connective tissue deposition in the aortic root. Chronic BEE supplementation in apoE-/- mice dose-dependently improves HDL function. Despite BEE promoting hyperlipidemia, which likely offsets HDL effects, BEE increases connective tissue content, suggesting improved atherosclerotic plaque stability.

Changes in lipid profile parameters and PON1 status associated with L55M PON1 polymorphism, overweight and exposure to tobacco smoke

Objective: The aim of our study was to investigate the effects of paraoxonase 1 (PON1) L55M polymorphism on the enzyme’s activity and concentration in the serum as well as its association with lipid profile parameters in a group of healthy persons. We also evaluated the presence of PON1 L55M polymorphism in a group of subjects exposed to tobacco smoke and with overweight or obesity on those parameters. Methods: Analysis of L55M polymorphism was done using polymerase chain reaction (PCR) and restriction fragment length polymorphism analysis (PCR – RFLP). Serum PON1 concentration and lipid profile parameters were assayed using commercial tests. PON1 activities were measured earlier elaborated procedures. Results: We observed a statistically significant difference in HDL and PON1 concentration: the highest in the LL genotype and the lowest in the MM genotype with the LM genotype having an intermediate concentration. L55M polymorphism influence on PON1 arylesterase and phosphotriesterase activity, whereas PON1 lactonase activity did not differ in all polymorphic variant groups. Exposure to tobacco smoke and overweight or obesity additionally disorder above mentioned parameters. Overweight and obesity in LM and MM genotype could be associated with higher PON1 phosphotriesterase activity. It is also possible that MM genotype could be a determinant of smoking addiction. Conclusions: L55M polymorphism, like exposure to tobacco smoke and overweight, disorders PON1 status and lipid profile parameters; therefore, it could be a crucial risk factor for the development of many metabolic disorders.

Activity of paraoxonase 1 (PON1) on HDL2 and HDL3 subclasses in renal disease

IntroductionCardiovascular complications, as the main cause of mortality in renal patients, are followed with altered lipoproteins composition. Considering that paraoxonase-1 (PON1) is an anti-oxidative enzyme located mainly on HDL particles, the current study has aim to investigate whether failure of kidney function leads to changes in the distribution of PON1 activity between different HDL subclasses. Materials and methodsIn 77 renal patients (21 chronic kidney disease (CKD) and 56 end stage renal disease (ESRD) patients on dialysis) and 20 healthy subjects PON1 activity on HDL2 and HDL3 subclasses was determined by zymogram method that combines gradient gel electrophoresis separation of HDL subclasses and measurement of PON1 activity in the same gel. ResultsSerum paraoxonase (p<0.01) and arylesterase activity (p<0.001) of PON1 as well as its concentration (p<0.01) were significantly lower in CKD and ESRD patients compared to controls. Relative proportion of HDL3 subclasses was higher in ESRD patients than in healthy participants, while HDL2 subclasses was significantly decreased in CKD (p<0.05) and ESRD (p<0.001) patients, as compared to controls. Furthermore, control subjects had higher PON1 activity on HDL2 (CKD and ESRD patients p<0.001) and HDL3 (CKD p<0.05; ESRD patients p<0.001) subclasses in comparison with the both patients groups. Also, significant negative correlation was found between paraoxonase activity of PON1 in serum and creatinine concentration (ρ=‐0.373, p<0.01). ConclusionsThis study showed that altered HDL subclasses distribution, changed PON1 activities on different HDL subclasses as well as diminished anti-oxidative protection could be important factors in atherosclerosis development in CKD and ESRD patients.

Arylesterase activity of Paraoxonase 1 - prognostic factor for one-year survival in patients with acute myocardial infarction

Abstract Introduction: Reduced serum levels of paraoxonase 1 (PON1) activities are associated with diseases involving increased oxidative stress, such as acute coronary syndrome. We aimed to determine whether serum PON1 activities are a prognostic factor for one-year survival following ST-elevation myocardial infarction (STEMI). Material and methods: We prospectively followed for one-year 75 patients diagnosed and treated for STEMI. Clinical, laboratory and imagistic data were gathered after coronary angiography. PON1 activities (paraoxonase, arylesterase, and lactonase) were assayed spectophotometrically on samples of heparinized plasma taken from the patients in a timeframe of maximum 20 minutes after coronary angiography. Results: Increased mortality was linked to age (patients over 68 years), permanent atrial fibrillation or left ventricular ejection fraction (LVEF) &lt;40% (associated with global hypokinesia, apical or septal akinesia), trivascular disease atherosclerosis, reduced PON1 activities (paraoxonase &lt;18.4 IU/mL, arylesterase &lt;12.6 IU/mL, lactonase &lt;27.6 IU/mL), and glomerular filtration rate levels &lt;54 mL/min/1.73m2. Multivariate survival analysis showed the independent prognostic role of age (HR 3.92; 95%CI 1.08-14.16; p=0.03), LVEF (HR 9.93; 95%CI 2.20-44.86; p=0.003) and arylesterase (HR 4.25; 95%CI 0.94-19.18; p=0.05) for one-year mortality. Conclusion: Reduced arylesterase activity of PON1 is an independent predictor of one-year survival after acute myocardial infarction.

Plasminogen Activator Inhibitor-1 Level Correlates with Lipoprotein Subfractions in Obese Nondiabetic Subjects.

Background The elevated level of plasminogen activator inhibitor-1 (PAI-1) in obese subjects with metabolic syndrome and in patients with type 2 diabetes is well established. The association of plasma PAI-1 and lipid metabolism is still unclear. The aim of the present study was to determine the relationship between plasma PAI-1 levels and the distribution of lipoprotein subfractions in obese and lean nondiabetic individuals. Subjects and Methods We enrolled fifty nondiabetic obese patients and thirty-two healthy volunteers. Lipoprotein subfractions were detected with Lipoprint System. Plasma PAI-1, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and myeloperoxidase (MPO) concentrations were determined with enzyme-linked immunosorbent assay (ELISA), while serum paraoxonase-1 (PON1) activities were measured by spectrophotometry. Results The TNF-α, IL-6, oxidized low-density lipoprotein (oxLDL), and MPO levels were found to be significantly higher, while PON1 paraoxonase and arylesterase activities were nonsignificantly lower in the obese patients. Strong significant negative correlations were found between plasma PAI-1 concentration and mean LDL size, as well as between PAI-1 concentrations and the levels of the large and intermediate high-density lipoprotein (HDL) subfractions. In multiple regression analysis, PAI-1 was predicted by waist circumference and intermediate HDL subfraction. Conclusion The significant correlations between PAI-1 levels and lipoprotein subfractions indicate the link between PAI-1 and lipid metabolism in obesity.

Paraoxonase 1 Q192R genotype and activity affect homocysteine thiolactone levels in humans.

Genetic or nutritional deficiencies in 1 carbon and homocysteine (Hcy) metabolism elevate Hcy-thiolactone levels and are associated with cardiovascular and neurologic diseases. Hcy-thiolactone causes protein damage, cellular toxicity, and proatherogenic changes in gene expression in human cells and tissues. A polymorphic cardio-protective enzyme, paraoxonase 1 (PON1), hydrolyzes Hcy-thiolactone in vitro. However, whether Hcy-thiolactone hydrolysis is a physiologic function of the PON1 protein and whether polymorphisms in the PON1 gene affect Hcy-thiolactone levels in humans was unknown. Here we show that the PON1-192 genotype, which affects the enzymatic activity of the PON1 protein, also affected urinary Hcy-thiolactone levels, normalized to creatinine. Carriers of the PON1-192R allele had significantly lower Hcy-thiolactone/creatinine levels than individuals carrying the PON1-192Q allele. Individuals with low serum PON1 paraoxonase activity had significantly higher Hcy-thiolactone/creatinine levels compared with individuals with high paraoxonase activity. In contrast, Hcy-thiolactone/creatinine levels were unaffected by serum PON1 arylesterase activity or by PON1 protein levels. Taken together, these findings suggest that PON1 hydrolyzes Hcy-thiolactone in humans and that the interindividual variations in PON1 genotype/activity can modulate the pathology of hyperhomocysteinemia.-Perła-Kaján, J., Borowczyk, K., Głowacki, R., Nygård, O., Jakubowski, H. Paraoxonase 1 Q192r genotype and activity affect homocysteine thiolactone levels in humans.

PON1 promoter polymorphisms contribute to PCOS susceptibility and phenotypic outcomes in Indian women

Polycystic ovary syndrome is a common endocrinopathy characterized by anovulatory infertility, hyperandrogenism, insulin resistance and oxidative stress, which predisposes affected women to reproductive and cardiometabolic complications in later life. We have investigated the association of PON1 promoter polymorphisms with PCOS susceptibility, PON1 activity and its related traits in Indian women. The genotypic and allelic frequency distribution of only −907G/C polymorphism in PON1 promoter showed significant difference between non-hyperandrogenic control and PCOS women, and was significantly associated with reduced susceptibility to PCOS, considering the recessive model. PON1 lactonase and arylesterase activities were also significantly decreased in women with PCOS compared to controls. Further, PON1 promoter polymorphisms were linked to altered insulin and testosterone levels in hyperandrogenic and non-hyperandrogenic women with PCOS. This study highlights PON1 as an important candidate gene influencing genetic pathophysiology of PCOS.