Paraoxonase 1 Phenotype Distribution Research Articles

Oxidative stress and phenotype frequencies of paraoxonase-1 in teratozoospermia.

Oxidative stress causes infertility in men by affecting especially sperm morphology. The aim of the study was to examine the frequencies of paraoxonase-1 (PON1) phenotypes and the serum PON1, arylesterase, total antioxidant status (TAS), total oxidant status (TOS), oxidative stress index, catalase and thiol levels in teratozoospermic infertile men and normospermic fertile men. The study included 184 teratozoospermic infertile men and 72 normospermic fertile men. The double substrate method was employed to determine the phenotype distribution of PON1. The evaluation of sperm morphology was made in accordance with the Kruger's criteria. TAS, catalase and thiol levels were determined to be significantly lower in teratozoospermic infertile men compared to normospermic fertile men. A significant change was not observed in the levels of TOS, PON1 and arylesterase. There was a positive correlation between catalase and thiol levels and sperm morphology. While there were significantly more teratozoospermic men with AA phenotypes compared to normospermic men, there were significantly more persons with AB and BB phenotypes in normospermic men than in teratozoospermic men. As far as we know, such a study was conducted for the first time and suggests that PON1 phenotypic distribution may play a significant role in sterile males because of impaired sperm morphology.

Paraoxonase and arylesterase levels in autoimmune thyroid diseases

Objective: The aim of this study was to evaluate serum paraoxonase-1 (PON1) activity and its association with oxidative stress in autoimmune thyroid disease (AITD).Methods: A total of 50 patients with AITD, including 25 with Hashimoto's thyroiditis and 25 with Graves’ disease were enrolled. The control group comprised 27 healthy subjects. Blood samples were obtained in the euthyroid period and 3 months after initiation of medical treatment. Serum samples from patients with AITD and the healthy control group were analyzed for basal PON1, salt-stimulated PON1, and arylesterase (ARE) activities, along with lipid hydroperoxide (LOOH) and total free sulfhydryl (–SH) levels.Results: Serum PON1 activities and –SH levels were significantly lower (P < 0.001, for each), whereas LOOH levels were significantly higher (P < 0.001, for each) in patients with AITD, compared to the control group. We observed no significant differences in ARE levels between the patient and healthy control groups (P > 0.05). PON1 activity was positively correlated with –SH (r = 0.522, P < 0.001) and negatively correlated with LOOH (r = −0.487, P < 0.001). PON1 phenotype distribution of the subjects was not significantly different among the three groups (P = 0.961).Conclusions: Serum PON1 activity is decreased in patients with AITD, and correlated positively with –SH, a well-known antioxidant, and negatively with LOOH, an index of lipid oxidation.

Higher serum lipids and oxidative stress in patients with normal tension glaucoma, but not pseudoexfoliative glaucoma.

This study entailed a cross-examination of oxidant/antioxidant balance, high-density lipoprotein (HDL)-linked paraoxonase 1 (PON1) phenotypes, and levels of serum routine lipids among patients with normal tension glaucoma (NTG) or pseudoexfoliative glaucoma (PEXG) compared with healthy control groups. We aimed to investigate the links between oxidative stress (OS), HDL-related antioxidant enzyme activities and dyslipidemia in distinct subtypes of glaucoma. The study included 32 patients with NTG, 31 patients with PEXG, and 40 control subjects. Levels of PON1 and arylesterase enzymatic activity, total oxidant status (TOS), and total antioxidant status were measured by spectrophotometry and OS indexes (OSI) were calculated. The phenotype distribution of PON1 was determined using the dual substrate method. Blood serum levels of HDL, low-density lipoprotein, total cholesterol (TC), and triglyceride (TG) were measured. The TOS and OSI values in the NTG group were significantly higher compared with the other groups (both p < 0.01). The phenotype distribution found in the glaucoma and control groups were NTG: QQ, 59.4%; QR, 37.5%; RR, 3.1%; PEXG: QQ, 45.1%; QR, 48.4%; RR, 6.5%; and in the control group: QQ, 42.5%; QR, 50.0%; RR, 7.5%. Serum TC levels were significantly higher than the control in both NTG and PEXG groups, whereas TG was significantly higher in NTG only (p < 0.01 and p < 0.02, respectively). Hyperlipidemia, OS and variations in phenotype distribution of PON1 may play a role in the pathogenesis of different types of glaucoma.

The Phenotype Distribution of Paraoxonase-1 in Patients with Multiple Myeloma, Bladder, and Colorectal Cancer

Abstract Background: Human serum paraoxonase-1 (PON1) shows wide variation among different ethnic groups around the world. The aim of the present study was to determine the phenotype distribution and enzymatic activity of PON1 and ARE (arylesterase) in colorectal cancer (CRC), bladder cancer (BC) and multiple myeloma (MM) patients compared to healthy subjects. Methods: A total of 160 subjects (40 CRC patients, 40 BC patients, 40 MM patients and 40 healthy controls) were admitted to the study. The phenotype distribution of PON1 was determined by using the dual substrate (paraoxon and phenylacetate) method. Results: PON 1 and ARE activities were significantly lower in the cancer patients compared to the control group. The following phenotype distributions were assessed in the cancer and control groups: MM: 52.5% (QQ), 40% (QR), 7.5% (RR); CRC: 52.5% (QQ), 40% (QR), 7.5% (RR); BC: 55% (QQ), 35% (QR), 10% (RR); and controls: 40% (QQ), 57.5% (QR), 2.5% (RR). Conclusions: We found that MM, CRC and BC patients were associated with lower PON1, ARE and stPON1 enzyme activities compared to the healthy subjects. However, PON1 phenotypes were similar between the cancer groups and control group.

Potential Association of Paraoxonase‐1, Type 2 Diabetes Mellitus, and Periodontitis

The association between periodontitis and systemic diseases, including cardiovascular diseases and diabetes mellitus (DM), has been recognized repeatedly. Paraoxonase-1 (PON-1) is involved in the prevention of atherosclerosis, and decreased enzyme activity in patients with DM has been shown. The aim of this study is to investigate a possible correlation between decreased PON-1 activity and the association between impaired glucose metabolism or DM and periodontitis. PON-1 phenotype distribution and enzyme activities were characterized by measuring the hydrolysis of phenylacetate and paraoxon in serum samples of 87 patients with type 2 DM and 46 patients with pre-DM showing impaired fasting plasma glucose and/or impaired oral glucose tolerance. The control group comprised 64 individuals with normal fasting plasma glucose and normal glucose tolerance. Altogether, 154 study participants were available for complete clinical periodontal examination. No difference in periodontitis prevalence existed between the study groups. However, patients with DM had an increased risk of suffering from generalized periodontitis (adjusted odds ratio = 4.05; 95% confidence interval = 1.24 to 13.18; P = 0.02), and their PON-1 activity was reduced compared to controls. In contrast, patients with pre-DM showed neither an increased periodontitis risk nor an impaired paraoxonase status. PON-1 was not associated directly with periodontitis. Nevertheless, concerning patients with DM, poor oral hygiene, male sex, and PON-1 phenotype were found to be significant predictors for periodontitis extent. Type 2 DM, but not a prediabetic state, increases the risk of generalized periodontitis. PON-1 status in patients with type 2 DM may contribute to this association.

Paraoxonase activity in healthy, diabetic, and hemodialysis patients

Paraoxonase 1 (PON1) is mainly complexed to HDL and is responsible, at least in part, for their antioxidant properties. The aims of our study were to determine the phenotype distribution and enzymatic activities of PON1 and the oxidative stress status of healthy subjects and diabetic and hemodialysis patients. PON1 paraoxonase and arylesterase activities and oxidative stress markers [malondialdehyde (MDA) and vitamin E levels] were measured in 300 individuals as a function of health status. The prevalence of the PON1 phenotypes in the study population was 74.51%, 18.15% and 7.34% for QQ, QR and RR, respectively. The phenotype distribution did not change significantly as a function of health status (healthy, diabetes, hemodialysis). However, the hemodialysis patients had lower PON1 paraoxonase and arylesterase activities than the diabetic patients and healthy subjects, while there were no significant differences between the diabetic patients and the healthy subjects. Oxidative stress markers (MDA levels and vitamin E/cholesterol ratio) were significantly higher in the diabetic and hemodialysis patients than in the healthy subjects. The lower plasma PON1 enzymatic activities in the hemodialysis patients was not associated with a difference in the phenotype distribution of PON1. Oxidative stress conditions were significantly higher in these patients, which may increase the risk of atherosclerosis in this population.

Relationship between PON1 phenotype and headache duration in migraine patients

The available data on the activity of paraoxonase-1 (PON1) in patients suffering from migraine without aura (MWoA) is scarce. The present study was conducted to fulfill the objective of investigating the probability of an association between PON1 phenotype distribution and headache duration in patients suffering from MWoA. Materials and methods: Seventy-six patients who suffer from MWoA and were not experiencing attacks at the time and 65 healthy volunteers were enrolled for the purpose of evaluation in the present study. Results: The levels of serum paraoxonase, arylesterase activities, and lipid hydroperoxide (LOOH) were determined for these subjects. The results obtained revealed that no statistical differences existed between the group suffering from MWoA and the control group with respect to the PON1 activity and the phenotype distribution (all values of P > 0.05), while the levels of serum LOOH were noted to be higher (P < 0.05) in the patient group. However, a significant relation was found between the PON1_{192}QR phenotype distribution and headache duration in patients suffering from MWoA (P < 0.001). It was observed that patients with the PON1_{192}QR (BB = homozygous high activity) polymorphism had headaches of shorter duration than patients with the PON1_{192}QQ (AA = homozygous low activity) and PON1_{192}QR (AB = heterozygous intermediate activity) polymorphisms. Along with these results, significant negative correlations were found between the ratio of salt-stimulated paraoxonase/arylesterase and headache duration (r: -0.40, P < 0.001) in patients suffering from MWoA in comparison to the control group. Finally, the activities of both paraoxonase and arylesterase were found to be inversely correlated with the levels of serum LOOH in the patient group [(r: -0.23, P < 0.05) and (r: -0.27, P < 0.05), respectively]. Conclusion: The results ascertained through the present study suggest that a significant correlation exists between PON1 phenotype distribution and headache duration in patients suffering from MWoA. Additionally, to the best of our knowledge, this is the first study to evaluate the association between PON1 polymorphism and headache duration in patients with migraine. PON1 phenotype distribution will play a key role in headache duration in patients with migraine.

No Association Between Serum Paraoxonase, Arylesterase Activities, and Hydatidiform Mole

In this study, we aimed to evaluate the association between hydatidiform mole (HM) and paraoxonase 1 (PON1) activity and phenotyping in comparison with healthy subjects (both pregnant and nonpregnant women). Eighty women were enrolled in this study. Of these, 26 had HM (group 1). Twenty-seven healthy women in the first trimester of pregnancy with a single viable fetus were included in the study as control subjects (group 2). The remaining 27 subjects were healthy nonpregnant women who also participated as control subjects (group 3). Paraoxonase and arylesterase activities were measured using commercially available kits (Relassay, Gaziantep, Turkey). Paraoxonase activity measurements were performed both in the absence (basal activity) and presence of NaCl (salt-stimulated activity). The phenotype distribution of PON1 activity was determined by the double-substrate method. Basal and salt-stimulated paraoxonase and arylesterase activities were not significantly different between the HM, healthy pregnant control, and healthy nonpregnant control groups. Hence, PON1 phenotype distribution of the subjects was not significantly different between these 3 groups. We determined no association between HM (complete or partial) and PON1 activity and phenotyping in comparison with pregnant and nonpregnant healthy subjects. Further studies including metastatic or invasive HM are needed.

Decreased human paraoxonase-1 activity in patients with Sjogren's syndrome

The aim of the study was to examine human serum paraoxonase 1 (PON1) activity, phenotype distribution and lipid parameters in patients with Sjögren's syndrome. The prevalence of cardio- and cerebrovascular diseases in SS patients was also evaluated after a 5-year follow-up. Fifty-seven SS patients and 17 age-matched healthy controls were enrolled into the study. PON1 and arylesterase activities were measured spectrophotometrically. The phenotype distribution of PON1 was determined by the dual-substrate method. Significantly lower PON1 activity was found in patients with SS compared with the control group (98.00 +/- 69.21 versus 203.3 +/- 92.78 U ml(-1); P < 0.001). There were significant differences in PON1 phenotype distribution of SS patients and controls (AA/AB/BB: 91.2/8.8/0 versus 58.8/29.4/11.8%; P < 0.01). No significant correlations were found between PON activity and disease-characteristic autoantibodies, including anti-Ro/SS-A and anti-La/SS-B concentrations. PON activity did not predict the cerebro/cardiovascular risk in SS patients during the 5-year follow-up. Despite the relatively small sample size that reduces the power of the study, decreased PON activity may be a possible cardiovascular risk factor in SS. Disadvantageous PON1 phenotype distribution may contribute to the decreased PON activity in these patients.

The human paraoxonase‐1 phenotype modifies the effect of statins on paraoxonase activity and lipid parameters

Human serum paraoxonase-1 (PON1) protects lipoproteins against oxidation by hydrolysing lipid peroxides in oxidized low-density lipoprotein, therefore it may protect against atherosclerosis. One of the two common PON1 gene polymorphisms within the PON1 gene is the Q192R, whose prevalence can be estimated by phenotype distribution analysis. The goal of this study was to clarify the role of PON1 phenotypes on the effect of three different statins on paraoxonase activity and lipid parameters. One hundred and sixty-four patients with type IIb hypercholesterolaemia were involved in the study. We examined the effect of 10 mg day(-1) atorvastatin, 10/20 mg day(-1) simvastatin and 80 mg day(-1) extended-release fluvastatin treatment on lipid levels and paraoxonase activity in patients with different PON1 phenotypes. The phenotype distribution of PON1 was determined by the dual substrate method. Three months of statin treatment significantly increased paraoxonase activity in every statin-treated group. In patients with AB+BB phenotype, statin treatment was significantly more effective on paraoxonase activity than in the AA group. Statin treatment more effectively decreased triglyceride levels in the AB+BB group compared with the AA group in the whole study population and in the simvastatin-treated group. Atorvastatin treatment was significantly more effective on apolipoprotein B levels in patients with AB+BB phenotype than in the AA phenotype group. The PON1 phenotype may be a novel predictive factor for the effectiveness of statin treatment on PON1 activity and serum lipid levels; however, different types of statins may exert different effects on these parameters.

Paraoxonase 1 phenotype distribution and activity differs in subjects with newly diagnosed Type 2 diabetes (the CODAM Study)

Paraoxonase 1 (PON1) is an antioxidant high-density lipoprotein-bound enzyme, which was recently found to be expressed in the islets of Langerhans. A substitution (Q/R) at position 192 results in enzymes with different activity. Oxidation has been implicated in the onset of diabetes, and it can be hypothesized that PON1 may have a protective effect on diabetes. Our aim was to compare PON1 activities and PON1 Q/R phenotypes in subjects with different degrees of glucose intolerance. We examined 566 members of the Cohort study of Diabetes and Atherosclerosis Maastricht (CoDAM), including subjects with normal glucose tolerance (NGT, n = 298), impaired glucose regulation (IGR, n = 128), newly diagnosed Type 2 diabetes (nDM, n = 78) and treated, that is to say known, Type 2 diabetes (kDM, n = 64). PON1 activity was measured in serum using paraoxon and diazoxon as substrates. The PON1 phenotype was determined using two-dimensional enzyme analysis. The RR-phenotype was significantly more frequent in nDM compared with NGT subjects (14.1 vs. 6.0%, P = 0.05). Adjusted for the PON1 phenotype, subjects with nDM had significant lower PON1 activity towards paraoxon and diazoxon than subjects with NGT. Adjusted odds ratios comparing the RR-variant with the QQ-variant were 2.17 [95% confidence interval (CI): 0.90-5.24] for impaired glucose tolerance, 2.84 (95% CI: 1.03-7.83) for nDM, 2.13 (95% CI; 0.61-7.42) for kDM and 2.65 (95% CI: 1.10-6.40) for total diabetes mellitus. An aberrant PON1 phenotype distribution and PON1 activity were observed in early diabetes. In addition, the higher state of oxidative stress may affect the future development of complications.