Serum Paraoxonase-1 Concentration Research Articles

Paraoxonase 1 and atrial fibrillation: Is there a relationship?

Atrial fibrillation (AF) is associated with oxidative stress and inflammation. Paraoxonase-1 (PON1), circulates in blood bound to high-density lipoproteins and reduces systemic oxidative stress. The aim of this study was to evaluate PON1 serum concentration and PON1 arylesterase activity (AREase) in patients with AF. We studied a group of 67 patients with symptomatic paroxysmal or persistent AF admitted for cardioversion and a control group of 59 patients without AF. Clinical parameters, lipid profile, PON1 concentration and AREase were evaluated. A significant difference in serum PON1 concentration and in AREase was found among the two groups. In a multivariate linear regression model, the presence of AF was associated with low PON1 concentration (P = .022). The body mass index was also independently associated with PON1 values (P < .001). Only the high-density lipoproteins-cholesterol level was independently associated with AREase (P = .002). PON1 serum concentrations and AREase were diminished in patients with AF, and the presence of AF was independently associated with low PON1 values.

Paraoxonase-1 Concentrations in Obstructive Sleep Apnoea: A Systematic Review and Meta-Analysis.

Obstructive sleep apnoea (OSA) is characterized by overproduction of reactive oxygen species and oxidative stress. The antioxidant enzyme paraoxonase-1 (PON-1) may be useful for monitoring the antioxidant defence systems and the effect of treatments in OSA patients. We investigated, by means of systematic review and meta-analysis, the serum concentrations of PON-1 in OSA patients and non-OSA controls. A literature search was conducted in PubMed, Web of Science, Scopus and Google Scholar databases, from the outset to November 2021, utilizing the terms: “paraoxonase” or “PON” or “paraoxonase-1” or “PON-1” and “obstructive sleep apnoea syndrome” or “OSAS” or “OSA”. Eleven studies in 429 OSA patients and 258 non-OSA controls were involved in the meta-analysis. The pooled serum PON-1 concentrations were significantly lower in OSA (standardized mean difference (SMD) = −0.70, 95% CI −1.13 to −0.28; p = 0.001). Despite the extreme between-study heterogeneity, the SMD values were not substantially affected by the sequential omission of individual studies. There was no publication bias. Our systematic review and meta-analysis supports the presence of an impaired antioxidant defence system in OSA, possibly the consequence of intermittent hypoxia. Further studies are required to determine the clinical use of PON-1 measurements for risk stratification and monitoring in OSA patients.

Serum Paroxonase 1 level may be an Indicator and Predictor of the Severity of Androgenetic Alopecia

Background:Androgenetic alopecia (AGA) is a common stressful form of hair loss caused by androgen excess, genetic factors, and exposure to oxidative stress (OS) with the formation of reactive oxygen species (ROS). Paraoxonase 1 (PON1) is an enzyme synthesized in the liver bound to high-density lipoproteins to prevent lipid peroxidation.Aim:The aim of our work is to estimate serum PON1 level in patients with AGA and correlate its levels with disease severity which may help in determining if there is a role of ROS in pathogenesis of AGA.Subjects and Methods:This study was carried out as a case and control on 40 patients with AGA (diagnosed by typical clinical and dermoscopic finding) versus 40 control subjects. Blood samples were taken from all subjects to assess serum PON1enzyme using enzyme-linked immunosorbent assay kits.Results:There was a significant decrease in serum PON1 concentration level in AGA patients in comparison to controls, in addition, there was a significant decrease correlated with AGA severity (P < 0,001). The study proved that PON1 is considered highly sensitive and specific for AGA cases and a good predictive factor of AGA in healthy subjects.Conclusion:This is the first study done to reveal that the level of PON1 significantly decreased in AGA patients, which may give additional proof that OS has role in the pathogenesis of AGA and hence may help in the management of AGA by adding antioxidants in treatment.

Evaluation of factors affecting sexual dysfunction in female patients with diabetes mellitus.

Our objective in this study was to evaluate the factors predicting female sexual dysfunction (FSD) in patients with diabetes mellitus (DM). The study included 149 women with DM. Sexual function was evaluated with the Female Sexual Function Index (FSFI) questionnaire, in which total scores under 26.55 characterized the occurrence of FSD (Group 1 > 26.55, Group 2 < 26.55). We recorded the patients' demographic, metabolic, and hormonal data. Ophthalmologic, neurologic, and renal complications were also evaluated. The antioxidant status of the patients in both groups was determined by measuring the activity of the enzymes paraoxonase-1 (PON-1) and arylesterase (ARE). Based on the FSFI scores, 60 patients were allocated to Group 1 (26.6 ± 12.3) and 89 to Group 2 (22.6 ± 9.5). Group 2 compared with Group 1 had significantly (p < 0.05) higher mean concentrations of glycated hemoglobin (HbA1c), glucose, triglycerides, and insulin, along with higher rates of metformin use, smoking, retinopathy, and nephropathy. The mean serum ARE concentrations were significantly lower in Group 2 compared with Group 1 (p = 0.000), but the mean serum PON-1 concentrations were similar between both groups (p = 0.218). On multivariable regression analysis, age, ARE activity, Beck Depression Inventory (BDI) score, and menopause were significant independent predictors of FSD (p < 0.05). In this study, we evaluated the predictive factors determining FSD caused by DM. Despite the significant results found in our study, future randomized controlled studies with a long follow-up and a larger number of patients are required to determine how DM affects FSD.

Paraoxonase-1 Serum Concentration and PON1 Gene Polymorphisms: Relationship with Non-Alcoholic Fatty Liver Disease.

Background: Non-alcoholic fatty liver disease (NAFLD) is an important cause of chronic liver diseases around the world. Paraoxonase-1 (PON1) is an enzyme produced by the liver with an important antioxidant role. The aim of this study was to evaluate PON1 serum concentration and PON1 gene polymorphisms in patients with NAFLD. Materials and methods: We studied a group of 81 patients with NAFLD with persistently elevated aminotransferases and a control group of 81 patients without liver diseases. We collected clinical information and performed routine blood tests. We also measured the serum concentration of PON1 and evaluated the PON1 gene polymorphisms L55M, Q192R, and C-108T. Results: There was a significant difference (p < 0.001) in serum PON1 concentrations among the two groups. The heterozygous and the mutated homozygous variants (LM + MM) of the L55M polymorphism were more frequent in the NAFLD group (p < 0.001). These genotypes were found in a multivariate binary logistic regression to be independently linked to NAFLD (Odds ratio = 3.4; p = 0.04). In a multivariate linear regression model, the presence of NAFLD was associated with low PON1 concentration (p < 0.001). Conclusions: PON1 serum concentrations were diminished in patients with NAFLD, and the presence of NAFLD was linked with low PON1 concentration. The LM + MM genotypes of the PON1 L55M polymorphism were an independent predictor for NAFLD with persistently elevated aminotransferases.

Serum Paraoxonase-1-Related Variables and Lipoprotein Profile in Patients with Lung or Head and Neck Cancer: Effect of Radiotherapy.

We investigated alterations in the levels of the antioxidant paraoxonase-1 (PON1) and the lipoprotein profile (analyzed by nuclear magnetic resonance) in patients with lung cancer (LC) or head and neck cancer (HNC), and the effects produced thereon by radiotherapy (RT). We included 33 patients with LC and 28 patients with HNC. Before irradiation, and one month after completion of RT, blood samples were obtained. The control group was composed of 50 healthy subjects. Patients had significantly lower serum PON1 activity and concentration before RT than the control group. PON1-related variables were good predictors of the presence of LC or HNC, with analytical sensitivities and specificities greater than 80%. Patients showed a significant increase in the number of particles of all subclasses of very-low-density lipoproteins (large, medium and small). However, these changes were not maintained when adjusted for age, sex, and other clinical and demographic variables. Irradiation was associated with a significant increase in PON1 concentration and, only in patients with HNC, with an increase in high-density lipoprotein-cholesterol concentration. Our results suggest that determinations of the levels of PON1-related variables may constitute good biomarkers for the evaluation of these diseases. Studies with a larger number of patients are needed to fully confirm this hypothesis.

Serum Paraoxonase-1 (PON1) Activity and Concentration: A new biomarker in Egyptian Patients with Liver Cirrhosis and Hepatocellular Carcinoma

Background and study aim: Hepatoma is the most common cancer worldwide, being regarded as the fifth of all malignancies. Mandating for a new, sensitive and specific markers for HCC are critically needed. Human paraoxonase-1 (PON-1), a Ca+2 dependent esterase in the liver, with antioxidant functions, and binds to the HDL particles and hence discarding carcinogenic lipid radicals as byproduct of lipid peroxidation. The aim of this study was to estimate the importance of serum PON-1 activity and concentration in HCC in Egyptian patients as a more sensitive and specific biomarker compared to an established biomarker; Alpha-fetoprotein (AFP). Patients and Methods: This study was conducted on 88 subjects: 64 patients; 40 patients with HCC, 24 cirrhotic patients and 24 healthy subjects who admitted in Internal Medicine Department, Suez CanalUniversityHospital, Ismailia, Egypt. Clinical and radiological investigations in those of the Cirrhotic, and HCC groups for viral hepatitis markers, liver function tests, serum assay of AFP and PON-1 activity and cconcentrations. Results: The results showed that PON-1 concentration was found significantly lower in HCC patients than those of the control and Cirrhotic group (p<0.001).The sensitivity and specificity of PON-1 concentration for HCC were superior to those of AFP and PON-1 activity especially in recently detected HCC. PON-1 concentration had a sensitivity of 88.3% and specificity of 90.48% at the optimal cut-off value of 70.55 (ng/ml). AFP gives a sensitivity of 82.50% and specificity of 73.08 at a cut-off 20.44 ng/ml. Conclusion: This study demonstrates that PON1 concentration and activity were superior to AFP in the recently detected HCC.

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.

Effect of continuous renal-replacement therapy on paraoxonase-1-related variables in patients with acute renal failure caused by septic shock

BackgroundAcute renal failure in patients with sepsis is associated with high mortality. Studies have highlighted alterations in serum paraoxonase-1 in severe infections. However, the published literature has no insight into the clinical evolution of these parameters in patients with sepsis and acute renal failure treated with extra-renal depuration techniques. MethodsWe studied 25 patients with sepsis and acute renal failure who were treated with continuous renal-replacement therapy. Blood for laboratory analyses was collected at days 0, 1, 2, 5, 7, and 10. We measured serum paraoxonase-1 activity and concentration, lipid profile, aminotransferase activities, pH, and lactate, urea, creatinine and C-reactive protein concentrations. Values were compared with those of 50 healthy individuals. ResultsPatients with sepsis and acute renal failure had lower serum paraoxonase-1 activity, lower high-density lipoprotein cholesterol concentrations, and higher serum paraoxonase-1 concentrations than the control group. We found a significant inverse correlation between serum paraoxonase-1 concentrations and the Acute Physiology And Chronic Health Evaluation II score in survivors as well as non-survivors, and a significant inverse correlation between serum paraoxonase-1 concentrations and the Sequential Organ Failure Assessment score only in survivors. Extra-renal depuration techniques produced a further increase in this enzyme related to the duration of treatment, and to serum urea concentration. ConclusionOur results show an inverse relationship between the concentration of paraoxonase-1 and the disease severity of patients with renal failure caused by septic shock. These results highlight relationships between paraoxonase-1 and infectious diseases and sepsis, with insights into potential clinical evolution of treatment.

Serum concentrations of trace elements and their relationships with paraoxonase-1 in morbidly obese women

The metabolic alterations associated with obesity include mineral dysregulation. Essential trace elements are nutrients with a relevant function in a large number of cellular processes and multiple roles in the correct functioning of metabolic enzymes. Paraoxonase-1 (PON1) is an antioxidant and anti-inflammatory enzyme that is compromised in obesity. In the present study, the potential alterations in trace elements in morbidly obese women were assessed in relation to serum PON1 activity and concentration, as well as to other obesity-related comorbidities such as diabetes mellitus and fatty liver. We recruited 41 morbidly obese women and 51 control individuals. The serum concentrations of 30 elements, PON1 paraoxonase and lactonase activities, and PON1 concentration were measured. We observed significant alterations in the levels of As, Ba, Cu, Ca, Fe, Mg, Na, Se, Sr, and Zn in obese women; some of them (As, Ca, Cr, Cu, Mg, and Se) being significantly correlated with serum PON1 values. The most relevant changes were observed in the concentrations of As, Sr and Mg, the last of which was also significantly associated with diabetes mellitus. The current results raise the possibility that increased ingestion and/or storage of a number of trace elements may be factors predisposing to obesity-related comorbidities and metabolic alterations.

Serum Paraoxonase-1 Concentration as a Potential Predictor of Urinary Bladder Cancer Recurrence. A Five Year Follow-Up Study

This study provides preliminary information on the usefulness of measuring serum paraoxonase-1 (PON1) concentration and activity (and other inflammatory markers) to predict tumor recurrence in patients with urinary bladder cancer. We studied a total of 39 hospitalized patients in whom the diagnosis of urinary bladder cancer was confirmed by transurethral resection. After five years of follow-up, 29 patients presented with tumor recurrence. As control subjects, we also studied 61 healthy subjects and a further 132 hospitalized patients who had a urinary catheter-related infection due to causes other than cancer. Results showed that urinary bladder patients had lower serum PON1 concentration and activity, and higher chemokine (C-C motif) ligand 2, C-reactive protein, and procalcitonin concentrations than the control individuals. Patients with tumor recurrence had significantly lower serum PON1 concentration than patients without tumor recurrence. The mean area under the curve of the receiver operating characteristics plot for serum PON1 concentration in discriminating patients with and those without tumor recurrence was 0.755 and the best combination of sensitivity and specificity was obtained at PON1=100mg/L (0.72 and 0.80, respectively). Establishing this value as a cut-off, positive predictive value was=0.91, and negative predictive value was=0.50. These results suggest that the measurement of serum PON1 concentration may be a high-sensitivity marker of tumor recurrence in urinary bladder cancer patients.

Effect of radiotherapy on activity and concentration of serum paraoxonase-1 in breast cancer patients.

Paraoxonase-1 (PON1) is an intra-cellular antioxidant enzyme found also in the circulation associated with high-density lipoproteins. The activity of this enzyme has been shown to be decreased in breast cancer (BC) patients. The aims of our study were to investigate the changes produced by radiotherapy (RT) on activity and concentration of serum PON1 in BC patients, and to evaluate the observed variations in relation to clinical and pathological characteristics of patients and tumors, and the response to treatment. We studied 200 women with BC who were scheduled to receive RT following excision of the tumor. Blood for analyses was obtained before and after the irradiation procedure. The control group was composed of 200 healthy women. Relative to control, BC patients had significantly lower serum PON1 activities pre-RT, while PON1 concentrations were at similar levels. RT was associated with a significant increase in serum PON1 activities and concentrations. We observed significant differences in serum PON1 concentrations post-RT between patients with luminal A or luminal B tumors. Serum PON1 concentration post-RT was markedly lower in BC patients with metastases. We conclude that benefit from RT accrues to the BC patients not only through its direct effect on cancer cells but also indirectly by improving the organism’s anti-oxidant defense mechanisms. In addition, our preliminary evidence suggests that the measurement of serum PON1 concentration post-RT could be an efficient prognostic biomarker, and may be used as an index of the efficacy of the RT.

BP.09.02] RELATION BETWEEN PARAOXONASE-1ACTIVITY AND PULSE PRESSURE IN PATIENTS WITH A ISCHEMIC STROKE

Objective: Stroke is a multifactorial disease arising from genetic andenvironmental risk factors or their interaction. The underlying cause of the majority of ischemic strokes is an atherosclerotic plaque in the carotid arteries. Oxidative stress and blood pressure were found to be closely related with cardiovascular and cerebrovascular diseases. Oxidative modification of serum low density lipoproteins (LDL) in the arterial wall is considered to be an important early step in the development of atherosclerosis. Paraoxonase-1 (PON1) has been considered as an anti-atherosclerosis factor, because it can reduce the oxidative modification of lipoproteins and macrophage foam cell formation occurring in the early phase of atherosclerosis. Therefore, it is easily inferred that the changes in serum PON1 concentrations or activity can affect vascular disease status. Elevated pulse pressure may lead to an increased risk of cardiovascular and cerebrovascular morbidity and mortality. We investigated the association between paraoxonase-1 (PON1) activities and pulse pressure (PP) in ischemic stroke patients.Design and method: We evaluated and compared the PON1 activity and PP in 46 ischemic stroke patients and 32 control patients. They were classified into 2 groups: Ischemic stroke patients (Group 1, n = 46), control patients (Group 2, n = 32). Blood pressure measurements were performed in all patients within 10 minutes admitted to emergency care unit. The PP was calculated by subtraction of diastolic blood pressure (DBP) from systolic blood pressure (SBP). Student t test and Chi-square analyses were used to compare differences between groups. Results: Hypertension, age, diabetes mellitus, dyslipidemia signficantly higher in ischemic stroke patients than control group (Table 1) (p < 0.05). PP was significantly higher in ischemic stroke patients than control group (48.12 ± 15.42 and 39.46 ± 12.56, p < 0.05). PON-1 activity was significantly lower in ischemic stroke patients than in control group (417,76 ± 79,72 and 432,34 ± 92,05 p < 0.05). Conclusions: Our results suggested that, PON-1 activity and PP are important risk factors in ischemic stroke patients.

The role of PON-1, GR, IL-18, and OxLDL in depression with and without posttraumatic stress disorder.

Both oxidative stress markers and inflammatory markers are important when diagnosing depression. Oxidative stress occurs due to an imbalance between free radical generation and antioxidant potential. Both adenosine triphosphate and reactive oxygen/nitrogen species are released during oxidative phosphorylation. When neuroinflammation and free radical production are increased, oxidative stress occurs and causes damage to all major cellular macromolecules. The aim of the study was to compare the concentrations of paraoxonase-1 (PON-1), glutathione reductase (GR), interleukin-18 (IL-18), and oxidized low-density lipoproteins (OxLDL) in depressed patients with and without posttraumatic stress disorder (PTSD), and PTSD alone. The number of participants was 460, including 230 males and 230 females. Each study group involved 60 subjects (30 males and 30 females). These were patients with mild depression (MD), moderate depression (MOD), severe depression (SeD), MD and PTSD (MD+PTSD), MOD and PTSD (MOD+PTSD), SeD and PTSD (SeD+PTSD), and with PTSD alone. The control group comprised 40 individuals (20 males and 20 females). At 7:00 a.m. all patients had blood samples collected to determine serum PON-1, GR, IL-18, and OxLDL concentrations using the ELISA test. Depression became more severe as GR, IL-18 and OxLDL concentrations increased and PON-1 concentrations decreased. All studied parameters can be considered markers of chronic stress in the above cases. They can be useful when making an early diagnosis and evaluating disease severity. Changes in the concentration levels of GR, IL-18, PON-1, and OxLDL may constitute a biological response to oxidative stress typical of depression.

Preliminary study on serum paraoxonase-1 status and chemokine (C-C motif) ligand 2 in hospitalized elderly patients with catheter-associated asymptomatic bacteriuria.

Urinary tract infections (UTI) are common among elderly patients in residential care facilities, as well as in the hospital setting. Identifying new biochemical markers of UTI is an active line of research since UTI management is resource intensive. Paraoxonase-1 (PON1) forms part of the patient's immune system, the response-to-injury and inflammation. Our study sought to evaluate alterations in inflammation-related paraoxonase-1 (PON1) and chemokine (C-C motif) ligand 2 (CCL2) in patients with an indwelling catheter to assess their potential usefulness as biomarkers of infection. Patients (n = 142) who had had the urinary catheter removed and 100 healthy volunteers were recruited. In all participants we measured serum PON1 activity, PON1 concentration, CCL2, procalcitonin and C-reactive protein (CRP). Results indicated that patients had higher CCL2, CRP and procalcitonin concentrations than the control group, and lower paraoxonase activity. There were no significant differences in PON1 concentrations. When comparing the diagnostic accuracy of CRP, procalcitonin, CCL2 and the PON1-related variables in discriminating between patients with and those without UTI, we found a considerable degree of overlap between groups, i.e., a low diagnostic accuracy. However, there were significant inverse logarithmic correlations between serum paraoxonase activity and the number of days the urinary catheter had been in situ. Our results suggest that measurement of these biochemical variables may be useful in investigating complications of long-term use of these devices and help to improve the economic and clinical investment required in the management of the often-associated infection.

Association of lipid profile with serum PON1 concentration in patients with chronic kidney disease

Patients with chronic kidney disease (CKD) are at high risk of atherosclerotic events; dyslipoproteinemia and the decrease of the HDL-linked enzyme paraoxonase 1 (PON1), might have a major role. This study intends to compare the association between lipid profile and serum PON1 levels in renal failure (RF) and hemodialysis (HD) patients. Serum lipids, HDL-subclasses and PON1 concentration were evaluated in 90 patients with CKD, divided into groups: RF (n = 46) and HD (n = 44), and in 30 normal individuals (control group). The results showed that PON1 was significantly lower in HD patients than in RF and controls (p < 0.001). In RF patients under statin therapy, PON1 did not differ from that of patients without statins. In HD patients without statins, PON1 was considerably low, whereas in HD with statins (30.42 ± 12.62 μg/mL) was lower than RF with statins (49.31 ± 14.94, p < 0.001). PON1 concentration was significantly and positively associated with HDL-C, HDL3-C and Apo A1 in all groups. Additionally, in HD patients PON1 was negatively associated with LDL-C. Multiple regression analysis revealed that LDL-C and statin treatment were independently related to PON1 concentration in HD patients (β = −0.331, p = 0.026 and β = 0.344, p = 0.020, respectively). In RF patients, HDL3-C and Apo A1 are strong determinants of PON1 levels. It is concluded that different parameters of lipid profile seem to affect serum PON1 concentration of RF and HD patients and probably contribute to the delay of atherosclerosis.

Effects of Iron Supplementation With and Without Docosahexaenoic Acid on the Cardiovascular Disease Risk Based on Paraoxonase-1, hs-CRP, and ApoB/ApoA-I Ratio in Women with Iron Deficiency Anemia.

Numerous studies have demonstrated that tissue deposition of iron following prolonged high dose of oral supplementation for treatment of iron deficiency anemia (IDA) leads to body iron overload and oxidative stress, which starts the process of atherosclerosis. This study aimed to determine the effect of iron supplementation in combination with docosahexaenoic acid (DHA) on the cardiovascular disease risk based on paraoxonase-1 (PON-1), high-sensitivity C-reactive protein (hs-CRP), and ApoB/ApoA-I ratio in women with IDA. In this randomized controlled trial, 76 women with IDA, aged 15-45years, were included. The patients were randomly assigned to receive 500mg of DHA supplement or placebo with an iron tablet, once daily for 12weeks. The participants were assessed by measurement of the serum iron, ferritin, PON-1, hs-CRP levels, and the ApoB/ApoA-I ratio at the beginning and end of study. Serum hs-CRP decreased in the DHA-supplemented group (p = 0.036), and ApoA-I decreased in the placebo group (p = 0.013). No significant difference was detected for the serum PON-1 concentration and the ApoB/ApoA-I ratio in two groups. Iron supplementation combined with DHA may have favorable effects on serum hs-CRP in women with IDA.

Association of serum paraoxonase concentration with serum lipid levels and bone mineral density measurements in early postmenopausal women

Objective To determine the association of serum paraoxonase concentration with serum lipid levels and bone mineral density in early postmenopausal Turkish women.Design One hundred healthy postmenopausal women were included in a cross-sectional study in a University hospital clinic. Blood was drawn from women who had bone mineral density (BMD) measurements during routine visits. BMD of the lumbar vertebrae was measured by dual-energy X-ray absorptiometry. The serum paraoxonase concentration and serum lipid levels were measured. Women were divided into two groups: those with normal lumbar vertebrae BMD and those with osteopenic lumbar vertebrae. Serum paraoxonase concentration was compared between the groups. The correlation between serum paraoxonase concentration and bone mass parameters was performed using Pearson's test.Results The paraoxonase concentration in the osteopenic group was significantly lower than in the group with normal lumbar vertebrae BMD. The paraoxonase concentration was moderately correlated with total cholesterol, low density lipoprotein cholesterol and triglyceride levels among early postmenopausal Turkish women.Conclusions Early postmenopausal women with osteopenic lumbar vertebrae have significantly lower paraoxonase concentration than those with normal lumbar vertebrae BMD. Further studies are needed to clarify the associations between the osteoporosis risk factors and paraoxonase concentration during late postmenopausal years.

Paraoxonase-1 gene Q192R and L55M polymorphisms and risk of cardiovascular disease in Egyptian patients with type 2 diabetes mellitus.

BackgroundIncreased oxidative stress or an impaired antioxidant defense mechanism may play a crucial role in the onset and progression of atherosclerosis. Recently, Paraoxonase −1 (PON1) which accounts for most of the antioxidant effect of high density lipoprotein (HDL) cholesterol has been presented as a potential therapeutic agent against atherosclerosis development. Allele frequencies for PON1 gene that influence enzyme concentration as well as activity differ greatly among ethnic groups and data from several studies showed ethnic variations in the interpretation of cardiovascular disease (CVD) associated with PON1 polymorphisms. In this work, we investigated PON1 Q192R and L55M polymorphisms in Egyptian patients with type 2 diabetes mellitus (T2DM) and its association with CVD.MethodsThe study included 184 subjects classified into 3 groups; T2DM, T2DM + CVD, and healthy controls. PON1 polymorphisms were genotyped by real-time PCR and PON1 concentration was assayed in serum by ELISA (enzyme linked immunesorbent assay).ResultsGenotype and allele frequencies of Q192R were significantly different between controls and diabetic patients. Frequency of QQ genotype was significantly higher in healthy controls, while QR and RR genotypes were significantly higher in diabetic patients (p = 0.02). Frequency of 55LL and LM genotypes were significantly higher in patients than in controls (p = 0.009). Q192R polymorphism associated with CVD in our diabetic patients (p = 0.01) and with low serum PON1 concentration (p = 0.04). Multiple logistic regression analysis revealed significant correlations between 192R and other independent CVD risk factors.ConclusionPON1 192R and 55 L alleles are associated with T2DM. Q192R polymorphism is associated with CVD and lower serum enzyme concentration and might represents a novel risk factor for CVD in Egyptian patients with T2DM.

Serum tumor necrosis factor-α, interleukin-6, monocyte chemotactic protein-1 and paraoxonase-1 profiles in women with endometriosis, PCOS, or unexplained infertility.

To investigate the serum levels of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), monocyte chemotactic protein-1 (MCP-1), and Paraoxonase-1 (PON-1) during fertility treatment of women with endometriosis (Endo), PCOS or unexplained infertility (Unexpl). Thirty-six patients with Endo, PCOS or Unexpl undergoing controlled ovarian stimulation for IVF or IUI were consented and their serum, on day-3 (baseline) and at the end of FSH treatment (peak), was collected and investigated for levels of TNF-α, IL-6, MCP-1, and PON-1. Correlations, ANOVA and Student's t-test were used for statistical analysis. Peak serum levels of IL-6, MCP-1 and PON-1 were positively correlated to E2 peak levels. TNF-α levels were inversely correlated to estradiol levels and they were lower in patients who ultimately became pregnant when compared to non-pregnant (P < 0.05). Mean TNF-α levels were significantly higher in Unexpl group (P < 0.05). The mean levels of IL-6, and MCP-1 were significantly (p < 0.05) higher in women with PCOS compared with Endo and Unexpl. No differences were found between the three clinical groups in patient's age, BMI, Day-3 FSH, PON-1 and pregnancy outcome. Circulating cytokine levels were influenced by ovarian stimulation, as demonstrated by increased levels of IL-6, MCP-1 and PON-1, and decreased level of TNF-α at the end of controlled ovarian stimulation. While evidence of relationship between circulating cytokines with mild endometriosis was not found, PCOS was associated with elevated serum IL-6 and MCP-1 but lower TNF-α concentration. Unexplained infertility was associated with elevated TNF-α level. No relationship between serum PON-1 concentration and PCOS, mild endometriosis or unexplained infertility was noted.