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Background: Diabetic nephropathy (DN) is currently the leading cause of end-stage renal disease globally. Oxidative stress which is classically defined as an event resulting from the magnitude of imbalance between oxidant and antioxidant substances, generated in a setting of oxidation-reduction reactions, and is hypothesized to play a role in the development of diabetic nephropathy. Aim and Objectives: The aim of the study was to assess lipid peroxidation by estimating serum malondialdehyde (MDA) and antioxidant status by assaying paraoxonase-1 (PON-1) in diabetes patients with nephropathy and healthy controls. Furthermore, the study aimed the correlation between MDA and PON-1 levels in patients with diabetic nephropathy. Materials and Methods: A cross-sectional comparative study was conducted in 152 participants, which were divided into two groups as control (n = 76) non-diabetic, healthy, age-, and sex-matched individuals and diabetic patients with nephropathy(n = 76). The study was conducted in Government Medical College, Kozhikode. All the subjects who satisfied the inclusion and exclusion criteria and who gave informed consent were included in a consecutive manner till sample size is achieved. Serum MDA and PON-1 were estimated using spectrophotometry. The data were analyzed using statistical package for the social sciences (SPSS) version 18. Results: Oxidative stress was increased in diabetic nephropathy patients as evidenced by significantly elevated MDA and reduced PON-1 than the normal controls. There was a significant negative correlation of serum MDA with serum PON-1 in patients with diabetic nephropathy. Conclusion: Oxidative stress is an important pathophysiological process for the development of diabetic nephropathy. This study reveals the importance of screening all diabetes patients for oxidative stress. Dietary management and antioxidant supplementation would help them to prevent development of diabetic nephropathy and related complications, which, in turn, improve their quality of life.
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Abstract Objective The aim of the present study was to examine the relation between the PON1 polymorphisms and recurrent pregnancy loss (RPL). Methods In a cross-sectional study, blood samples were collected from 100 females. DNA was extracted and PON1 genotypes were determined by polymerase chain reaction (PCR) amplification. Results Regarding PON1 L55M, the mutated allele (M) frequency was found in 70.5% in RPL and in 53.5% in controls; theMallele was significantly associated with an increased risk of RPL (adjusted odds ratio [ORadj]=2.07; 95% confidence interval [CI]; p<0.001). However, regarding PON1 Q192R, the R mutated allele frequency was found in 28.5% in RPL and in 33% in controls. The R allele did not show any risk for RPL (ORadj 0.81; 95%CI; p=0.329). Conclusion The present study suggests that there is an effect of genetic polymorphism on RPL and provides additional evidence that combines with the growing information about the ways in which certain PON1 genotypes can affect the development of the fetus in the uterus.
Resumo Objetivo O objetivo deste estudo foi examinar a relação entre os polimorfismos PON1 e perda recorrente de gravidez PRG. Métodos Em um estudo transversal, foramcoletadas amostras de sangue de 100 mulheres. O DNA foi extraído e os genótipos PON1 foram determinados por amplificação por PCR. Resultados Com relação ao PON1 L55M, a frequência do alelo mutado (M) foi encontrada em 70,5% no PRG e em 53,5% nos controles; o alelo M foi significativamente associado a um risco aumentado de PRG (odds radio ajustado [ORadj] =2,07; intervalo de confiança [IC] 95%; p<0,001). No entanto, em relação ao PON1 Q192R, a frequência do alelo mutado R foi encontrada em 28,5% no PRG e em 33% nos controles. O alelo R não mostrou qualquer risco para PRG (ORadj 0,81; IC 95; p=0,329). Conclusão O presente estudo sugere que há um efeito do polimorfismo genético sobre PRG e fornece evidências adicionais que se combinam com as informações crescentes sobre asmaneiras pelas quais certos genótipos PON1 podemafetar o desenvolvimento do feto no útero.
Subject(s)
Humans , Female , Pesticides , Abortion, Habitual/genetics , Polymorphism, Genetic , Cross-Sectional Studies , Aryldialkylphosphatase/geneticsABSTRACT
ABSTRACT Purpose: Paraoxonase-1 activity is associated with age-related macular degeneration. Two polymorphisms (L55M and Q192R) were shown to increase paraoxonase-1 activity and have been implicated in the development of age-related macular degeneration. The results of studies that have examined these polymorphisms are conflicting, showing no effect, as well as increased or decreased risk. Therefore, this meta-analysis was conducted to determine the effect of these polymorphisms on age-related macular degeneration. Methods: PubMed, EBSCO, LILACS, and Scopus databases, as well as and the retrieved bibliographies of publications were searched for case-control studies that examined for paraoxonase-1 polymorphisms and age-related macular degeneration. Data were analyzed using the Comprehensive Meta-Analysis Version 2.2 and the NCSS Statistical Version 2020 software. Genotype distributions were extracted and, depending on the level of heterogeneity, fixed effects or random effects models were used to calculate pooled odds ratios (ORs) with 95% confidence intervals (95% CIs) for the heterozygous, homozygous, dominant, recessive, and allelic genetic models. Results: Overall, for the L55M polymorphism, none of the genetic models demonstrated a significant association. However, for non-Asian populations, a significant association was determined for the heterozygous and dominant genetic models (ORrange=1.24-1.27, p<0.05). For the Asian population, the heterozygous, dominant, and allelic genetic models demonstrated a benefit/protective factor (ORrange=0.29-0.35, p<0.05). For the Q192R polymorphism, none of the genetic models demonstrated a significant association. However, when the cohort was grouped by ethnicity, a significant association was determined in the Asian population for the recessive and allelic genetic models (ORrange=1.63-2.08, p<0.05). However, for the non-Asian population, there was no association observed. Also, there was no identifiable risk when the cohort was stratified into exudative and non-exudative cases. Conclusions: The paraoxonase-1L55M polymorphism increases the risk of developing age-related macular degeneration in non-Asian populations, whereas in Asian populations, the polymorphism exerts a protective effect. However, for the paraoxonase-1 Q192R polymorphism, only the Asian population demonstrated a risk of developing age-related macular degeneration.(AU)
RESUMO Objetivo: A atividade da paraoxonase1 está associada à degeneração macular relacionada à idade. Dois polimorfismos (L55M e Q192R) mostraram aumentar a atividade da paraoxonase1 e foram implicados no desenvolvimento da degeneração macular relacionada à idade. Os estudos que examinaram esses polimorfismos apresentaram resultados conflitantes: nenhum efeito, risco aumentado ou diminuído. Assim, esta meta-análise foi realizada para determinar o efeito desses polimorfismos na degeneração macular relacionada à idade. Métodos: Foi feita uma busca nos bancos de dados PubMed, EBSCO, LILACS e SCOPUS, bem como nas bibliografias compiladas das publicações, buscando-se estudos caso-controle que tivessem analisado os polimorfismos da paraoxonase1 e a degeneração macular relacionada à idade. Os dados foram analisados com software Comprehensive Meta-Analysis, versão 2.2, e NCSS Statistical, versão 2020. As distribuições de genótipos foram extraídas e, dependendo do nível de heterogeneidade, modelos de efeitos fixos ou aleatórios foram utilizados para calcular razões de probabilidade (RPs) combinadas, com intervalos de confiança de 95% (IC 95%) para os modelos genéticos heterozigoto, homozigoto, dominante, recessivo e alélico. Resultados: Em geral, nenhum dos modelos genéticos demonstrou associação significativa para o polimorfismo L55M. Entretanto, em populações não asiáticas, foi determinada uma associação significativa para os modelos genéticos heterozigoto e dominante (RPfaixa=1,24-1,27, p<0,05). Para a população asiática, os modelos heterozigoto, dominante e alélico mostraram um fator benéfico ou protetor (RPfaixa=0,29-0,35, p<0,05). Para o polimorfismo Q192R, nenhum dos modelos genéticos demonstrou qualquer associação significativa. Porém, quando a coorte foi agrupada por etnia, determinou-se uma associação significativa na população asiática para os modelos genéticos recessivo e alélico (RPfaixa=1,63-2,08, p<0,05). Contudo, nenhuma associação foi observada para a população não asiática. Não houve risco identificável quando a coorte foi estratificada em exsudativa e não exsudativa. Conclusões: Determinamos que o polimorfismo L55M da paraoxonase1 de fato aumenta o risco de desenvolvimento de degeneração macular relacionada à idade em populações não asiáticas, enquanto que em populações asiáticas, esse polimorfismo tem um efeito protetor. Porém, para o polimorfismo Q192R da paraoxonase1, apenas a população asiática demonstrou risco de desenvolver degeneração macular relacionada à idade.(AU)
Subject(s)
Humans , Polymorphism, Genetic , Aryldialkylphosphatase , Macular Degeneration/etiology , EthnicityABSTRACT
Objective: Paraoxonase 1 (PON1) plays a defensive role against oxidative stress by destroying oxidized lipids. Q192R single nucleotide polymorphism of PON1 gene alters the enzyme's activity. Several investigations reported a link between Q192R and an increased risk of developing tumors including uterine leiomyomas. We assessed the antioxidant effects of Q192R on myoma which fluctuate in frequency between populations. Study Design: The cohort consisted of 68 unrelated uterine leiomyoma patients and 93 healthy controls that were randomly selected from women with no ultrasonographic evidence of myoma. Materials and Methods: Genotyping was performed using tetra-primer amplification refractory mutation system-polymerase chain reaction. Chi-square test was selected to evaluate differences between the groups. Results: To analyze the correlation between PON1 Q192R and leiomyoma risk, the AA genotype was given as a reference genotype then the two other genotypes were compared with the reference. A significantly (P < 0.05) increased risk of myoma was observed with both Q192R homozygote GG and heterozygote AG genotypes. The odds ratio (OR) of AG genotype was calculated 1.8 (confidence interval [CI]: 0.94–3.62). A higher OR was seen with GG genotype (OR: 2.8; 95% CI: 0.98–8.18). Conclusion: Oxidative stress has been suspected of having a link with tumor development, and the role of endogenous-free radical scavenger is taken into consideration. Increased protein oxidative stress status and reduced antioxidant capacity have been observed in leiomyomas patients. Our study indicates that the low-antioxidant PON1 R192 allele correlates to leiomyoma development
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Background: Birth defects are conditions of prenatal origin that are present at birth, potentially impacting an infant's health, development, and/or survival. Several environmental toxins affect the growth of the fetus during the intrauterine period by affecting various cellular components. Pesticides and industrial chemicals are known toxins that can hinder the developmental process. In this study, authors are evaluating the relation of cholinesterase and paraoxonase-1 with visible congenital anomalies.Methods: Sixty babies delivered in the labor room were selected for the study. They were divided into two groups. Thirty newborns with visible congenital anomalies were included in Group I. Only babies with visible congenital anomalies were taken as inclusion criteria for this group. This group was compared with Group II, which were taken as controls and consisted of 30 healthy newborns without any congenital anomalies. Serum cholinesterase and serum paraoxonase-1 were estimated and statistical tests were applied.Results: Serum cholinesterase and serum paraoxonase-1 were significantly low in the babies with visible congenital anomalies. Serum cholinesterase levels showed a statistically significant positive correlation with serum paraoxonase 1 level in both the groups.Conclusions: Decrease in acetylcholinesterase by various environmental toxins and the associated decrease in serum paraoxonase level imposes significant oxidant stress and the resultant risk of developing congenital anomalies.
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Abstract Objective: The 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. Methods: This 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%. Results: In 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, 15-30 U/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. Conclusions: During 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.
Resumo Objetivo: A enzima cardioprotetora Paraoxonase 1 (PON1) sofre importante influência de polimorfismos genéticos e fatores nutricionais. O objetivo deste estudo foi investigar a influência da alimentação, do estado nutricional e do polimorfismo C(-107)T sobre a atividade arilesterase da PON1 em crianças. Métodos: Estudo transversal com 97 crianças entre 5 e 8 anos, de ambos os sexos, de um ambulatório de pediatria no sul do Brasil. Realizou-se questionário sociodemográfico, de comportamento e de consumo alimentar, medidas antropométricas e coleta de sangue em laboratório. A atividade arilesterase da PON1 foi mensurada pela extinção de fenol (U/mL), realizada extração do DNA e análise do polimorfismo PON1 C(-107)T. O equilíbrio de Hardy-Weinberg foi testado com qui-quadrado e usada regressão linear para estimar a atividade da PON1 segundo quatro modelos de ajuste, erro aceitável de 5%. Resultados: Na amostra o sexo masculino representou 50,5%, 39,2% tinham 6 anos, 54,5% eram eutróficos e 51,5% tinha atividade da PON1 inferior à mediana (90,0;15-30 U/ml). A frequência dos genótipos foi 54,6% (53/97), 31,0% (30/97) e 14,4% (14/97), respectivamente, para CT, CC e TT, estiveram em equilíbrio de Hardy-Weinberg (p = 0,22). Na análise de regressão o modelo que incluiu variáveis sociodemográficas, de frequência do consumo de frutas, verduras, legumes, laticínios e feijões estimou uma variabilidade de 14,8% na atividade da PON1 combinada ao polimorfismo PON1 C(-107)T. Conclusões: Na infância uma alimentação de boa qualidade, com maior participação de alimentos saudáveis foi importante para predizer a atividade da enzima cardioprotetora PON1 combinada ao polimorfismo C(-107)T do gene da PON1.
Subject(s)
Humans , Male , Female , Child, Preschool , Child , Polymorphism, Genetic/genetics , Aryldialkylphosphatase/genetics , Brazil , Cross-Sectional Studies , GenotypeABSTRACT
Background: Diabetic peripheral sensorimotor polyneuropathy is the most common complication seen in patients with diabetes mellitus (DM). Oxidant system plays a crucial role in its physiopathology. We investigated the changes in the serum levels of total antioxidant status (TAS), total oxidant status (TOS), paraoxonase-1 (PON1) and oxidative stress index (OSI) to evaluate the antioxidant efficacy of alpha lipoic acid (ALA) and/or gabapentin in patients with diabetic polyneuropathy (DPN).Methods: Sixty-three type 2 DM patients with diabetic polyneuropathy (DPN) were enrolled in the study. Patients with DPN were divided into four groups in terms of their treatment: Group 1 consisted of treatment-naive patients; patients treated with ALA, gabapentin or combination of ALA and gabapentin comprised groups 2, 3, and 4, respectively. The patients received the medications for at least six weeks. Serum levels of TAS, TOS, PON1 and OSI were analyzed.Results: No significant difference was observed between the groups according to the oxidative stress parameters studied.Conclusions: The use of ALA and/or gabapentin in patients with DPN did not significantly affect the oxidative stress parameters, including TAS, TOS, PON1, and OSI.
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ABSTRACT Objective Our objective in this study was to evaluate the factors predicting female sexual dysfunction (FSD) in patients with diabetes mellitus (DM). Subjects and methods 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). Results 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). Conclusions 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.
Subject(s)
Humans , Female , Adult , Aged , Aged, 80 and over , Young Adult , Sexual Dysfunction, Physiological/etiology , Diabetes Complications , Diabetes Mellitus , Prevalence , Surveys and Questionnaires , Risk Factors , Middle AgedABSTRACT
Objective@#To explore the prognostic value of serum paraoxonase-1(PON-1) in patients with non-muscle-invasive bladder cancer.@*Methods@#Serum levels of paraoxonase-1 (PON-1) in one hundred and twenty non-muscle-invasive bladder cancer patients (bladder cancer group) and fifty healthy controls (healthy control group) in Hankou Hospital of Wuhan were detected using spectrophotometric rate assay with p-nitrophenol as the substrate. The overall survival and disease-free survival curve was drawn by Kaplan-Meier method in different serum PON-1 levels, and independent prognostic factors were analyzed by Cox proportional hazards model.@*Results@#The serum levels of PON-1 in bladder cancer group was (116.52 ± 21.91) U/L, in healthy control group was (237.96 ± 46.97) U/L, and there was significant difference (t=23.004, P < 0.01). The patients in bladder cancer group were divided into high PON-1 group (≥ 116.52 U/L, 64 patients) and low PON-1 group (< 116.52 U/L, 56 patients) by the median of PON-1(116.52 U/L). Serum PON-1 levels were closely correlated with age of bladder cancer patients (P < 0.05), but not correlated with gender, Karnofsky score, anesthesia risk grading(ASA grade), tumor multiplicity, T stage, pathological grade and tumor size (P > 0.05). The median over-all survival time of the high PON-1 group was 62 months, and 52 months in the low PON-1 group, and there was significant difference (Log-rank=7.004, P=0.008). The median disease-free survival time of the high PON-1 group was 57 months, and 49 months in the low PON-1 group, and there was significant difference (Log-rank=4.068, P=0.044). Cox multivariate regression analysis showed that T stage, serum PON-1 levels was independently associated with overall survival and disease-free survival of patients with non-muscle invasive bladder cancer (P < 0.05).@*Conclusions@#Serum PON-1 levels is increased in non-muscle invasive bladder cancer patients, and PON-1 is an independent prognostic indicator of overall survival and disease-free survival in patients with bladder cancer.
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Objective To explore the prognostic value of serum paraoxonase-1(PON-1) in patients with non-muscle-invasive bladder cancer. Methods Serum levels of paraoxonase-1 (PON-1) in one hundred and twenty non-muscle-invasive bladder cancer patients (bladder cancer group) and fifty healthy controls (healthy control group) in Hankou Hospital of Wuhan were detected using spectrophotometric rate assay with p-nitrophenol as the substrate. The overall survival and disease-free survival curve was drawn by Kaplan-Meier method in different serum PON-1 levels, and independent prognostic factors were analyzed by Cox proportional hazards model. Results The serum levels of PON-1 in bladder cancer group was (116.52 ± 21.91) U/L, in healthy control group was (237.96 ± 46.97) U/L, and there was significant difference (ti23.004, P < 0.01). The patients in bladder cancer group were divided into high PON-1 group ( ≥116.52 U/L, 64 patients) and low PON-1 group (< 116.52 U/L, 56 patients) by the median of PON-1(116.52 U/L). Serum PON-1 levels were closely correlated with age of bladder cancer patients (P < 0.05), but not correlated with gender, Karnofsky score, anesthesia risk grading( ASA grade), tumor multiplicity, T stage, pathological grade and tumor size (P > 0.05). The median over-all survival time of the high PON-1 group was 62 months, and 52 months in the low PON-1 group, and there was significant difference (Log-ranki7.004, Pi0.008). The median disease-free survival time of the high PON-1 group was 57 months, and 49 months in the low PON-1 group, and there was significant difference (Log-ranki4.068, Pi0.044). Cox multivariate regression analysis showed that T stage, serum PON-1 levels was independently associated with overall survival and disease-free survival of patients with non-muscle invasive bladder cancer (P < 0.05). Conclusions Serum PON-1 levels is increased in non-muscle invasive bladder cancer patients, and PON-1 is an independent prognostic indicator of overall survival and disease-free survival in patients with bladder cancer.
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Objective@#To investigate the effects of miRNA on the expression of paraoxonase 1 (PON1) and its clinical application in the patients with nonalcoholic steatohepatitis (NASH). @*Methods@#Bioinformatics methods were used to analyze and predict PON1 related regulation on miRNA. PON1 luciferase reporter gene vectors were constructed and the activity of dual luciferase was analyzed. The up/down-regulated levels of miRNA in HepG2 cells of different groups were detected by real-time fluorescence quantitative PCR (qRT-PCR), and the levels of PON1 protein in HepG2 cells were detected by western blot. The levels of miR140-5p in the serum of healthy people and NASH patients were also analyzed by qRT-PCR. @*Results@#According to the prediction of TargetScan database, miR140-5p may bind complementarily to the end of PON13′-UTR. The analysis for the activity of dual luciferase reporter gene showed that miR-140-5p mimic significantly downregulated the fluorescence of wild type PON1 vector (P＜0.01). The results of qRT-PCR demonstrated that miR-140-5p mimic group showed high overexpression (P＜0.01) compared with the normal cell control group and the negative mimic control group, while miR-140-5p inhibitor group appeared corresponding low expression (P＜0.05). western blot results suggested that the transfection of miR140-5p mimic significantly down-regulated the expression of PON1 (P＜0.01) while miR140-5p inhibitor up-regulated this expression (P＜0.01). Compared with the healthy control group, the level of miR140-5p was decreased in the serum of NASH patients, and the difference was statistically significant (P＜0.01). @*Conclusion@#miR140-5p may be involved in the progression of nonalcoholic steatohepatitis through regulation for the posttranscriptional gene expression of PON1.
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<p><b>Objective</b>To investigate the correlation between the single nucleotide polymorphism (SNP) rs662 of the paraoxonase 1 gene (PON1) and the risk of male infertility.</p><p><b>METHODS</b>This case-control study included 403 male idiopathic infertility patients aged 29.00 ± 4.48 years in the case group and 329 normal fertile men aged 28.28 ± 4.08 years as healthy controls. We obtained DNA from the peripheral venous blood of the subjects, genotyped the SNP rs662 of PON1 by Sequenom MassArray, and analyzed the association between different genotypes of PON1 rs662 and male infertility using the logistic regression model.</p><p><b>RESULTS</b>Compared with the normal controls, the infertility patients showed a significantly increased level of follicle-stimulating hormone (FSH) (［16.30 ± 17.76］ vs ［4.72 ± 2.51］ U/L, P < 0.01) but a decreased percentage of progressively motile sperm (PMS) (［7.40 ± 14.17］ % vs ［41.93 ± 9.06］ %, P < 0.01) and sperm concentration (［2.74 ± 3.64］ vs ［75.83 ± 63.66］ ×10⁶/ml, P < 0.01). Statistically significant differences were not found in the other parameters between the two groups of subjects, nor in the correlation of male infertility with the heterozygous genotype GA versus the wild homozygous genotype GG (OR = 0.98, 95% CI: 0.63－1.53, P = 0.923) or the homozygous genotype AA versus the wild homozygous genotype GG (OR = 0.87, 95% CI: 0.56－1.34, P = 0.525).</p><p><b>CONCLUSIONS</b>The SNP rs662 of PON1 was not correlated with male infertility, which, however, needs to be confirmed by further studies with larger samples from a larger area.</p>
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Objective To investigate the correlation between Paraoxonase-1 (PON-1) gene Q192R polymorphism and clopidogrel resistance (CR). Methods A total of 118 patients with coronary artery disease diagnosed by coronary angiography or coronary artery CT angiography were enrolled. Platelet aggregation rate was assessed by ADP-induced light-transmittance aggregometry after the patients received adequate clopidogrel pretreatment.The patients were divided into (clopidogrel resistance group (CR group) and non-clopidogrel resistance group (NCR group) according to the ADP-induced platelet aggregation rate. The gene of Q192R was detected by MassARRAY Time of Flight Mass Spectrometry.The genotypes and allele frequencies between the two groups were compared. Results According to the ADP-induced platelet aggregation rate,25 patients were defined as clopidogrel resistant and 93 as non-clopidogrel resistant.The incidence of clopidogrel resistance was 21.2％.Three frequencies of genotype RR,QR and QQ were 36. 0％,52. 0％ and 12. 0％ in CR group, and 32. 2％,57. 0％ and 10. 8％ in NCR group, respectively.The frequencies of Q and R allele in CR group were 62.0％ and 38.0％,and those in NCR group were 60.8％ and 39.2％.No significant differences in genotype and allele frequency were found between CR group and NCR group (P>0.05). Conclusion The PON-1 gene Q192R polymorphism is not associated with clopidogrel resistance in patients with CHD.
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Objective·To investigate whether paraoxonase 1 (PON1) genotypes were effect modifiers in the relationship between exposure to organophosphate pesticides (Ops) and oxidative stress level in pregnant women.Methods · A total of 204 pregnant women recruited from a hospital in Shandong Province were included in the study.Four nonspecific dialkyl phosphate (DAP) metabolites of Ops were measured in each urine sample.Levels of two oxidative stress biomarkers [total free sulfhydryl (-SH) and malondialdehyde (MDA)] were measured in serum samples.Blood samples were also analyzed for detecting PON1 genotypes (PONI-108,PON1192 and PON155).Separate linear regression models were conducted to explore the relationship between DAP metabolite levels and oxidative stress levels in all 204 pregnant women or women within each PON1 genotype.Results· There was no significant association between DAP metabolite levels and oxidative stress levels in all 204 women.Levels of dimethyl phosphates [β (95％ CI):-104.10 (-191.31,-16.88)] and dialkyl phosphates [f (95％ CI):-111.78 (-221.84,-1.72)] were negatively associated with-SH level among pregnant women with PON1192RR genotype,but this association was not found among women with other genotypes.Conclusion· OP exposure may be associated with a higher oxidative stress level among pregnant women with PONI192RR genotype.
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Objective: To investigate whether paraoxonase 1 (PON1) genotypes were effect modifiers in the relationship between exposure to organophosphate pesticides (OPs) and oxidative stress level in pregnant women. Methods: A total of 204 pregnant women recruited from a hospital in Shandong Province were included in the study. Four nonspecific dialkyl phosphate (DAP) metabolites of OPs were measured in each urine sample. Levels of two oxidative stress biomarkers [total free sulfhydryl (-SH) and malondialdehyde (MDA)] were measured in serum samples. Blood samples were also analyzed for detecting PON1 genotypes (PON1-108, PON1192 and PON155). Separate linear regression models were conducted to explore the relationship between DAP metabolite levels and oxidative stress levels in all 204 pregnant women or women within each PON1 genotype. Results: There was no significant association between DAP metabolite levels and oxidative stress levels in all 204 women. Levels of dimethyl phosphates [β (95% CI): -104.10 (-191.31, -16.88)] and dialkyl phosphates [β (95% CI): -111.78 (-221.84, -1.72)] were negatively associated with -SH level among pregnant women with PON1192RR genotype, but this association was not found among women with other genotypes. Conclusion: OP exposure may be associated with a higher oxidative stress level among pregnant women with PON1192RR genotype.
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Objective To explore whether the use of purified rabbit serum paraoxonase 1 (PON1) for the treatment of dichlorvos-induced liver injury in rats is superior to traditional method.Methods Thirty male SD rats were randomly divided into the followint 5 groups,with 6 rats in each group:control group (A group),dichlorvos group (B group),traditional treatment group (C group),PON 1 treatment group (D group),combined treatment group (E group).Rats in groups B,C,D and E were adminstered dichlorvos by intraperitoneal injection 9 mg/kg.In group C,atropine 10 mg/kg and iodine solution 45 mg/kg were injected intraperitoneally within 2 min after dichlorvos administration.In group D,PON1 was injected intravenously at a dose of 9 600 U/kg,30 min prior to poisoning.In group E,PON1 was injected intravenously at a dose of 9 600 U/kg,30 min prior to poisoning,followed by in travenous injection of atropine 10 mg/kg and iodine solution 45 rng/kg within 2 min after poisoning.Rats in A group received normal saline.Blood was collected at different time points to examine the acetyl cholinesterase (AChE)-levels by ELISA method.Liver tissue were collected at 12 hours after model establishment to observe the pathological changes.The expression of 4 hydroxy 2-nonenal (4-HNE) in the liver tissue was detected by immunohistochemistry and Western blotting.Results In group B,AChE levels decreased significantly,liver cells showed severn fatty degeneration,karyopyknosis and other pathological changes,and 4-HNE expression increased.The pathological changes of group D and group E were less obvious than those of group C,and the 4-HNE expression in the group D and group E were significantly different from that in the group C (P＜ 0.05).Conclusion PON1 plays a protective role in dichlorvos-induced liver injury in rats,and this protection is better than that offered by traditional treatment.
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Objective To observe the effect of paraoxonase 1 (PON1) application of the new method of arylesterase activity in patients with coronary heart disease,analysis of paraoxonase 1 (PON1) of the clinical value of arylesterase activity in the new testing method.Methods From January 2014 to January 2016 in our hospital 86 patients with coronary heart disease as the research object,and then select the healthy people at the same time to the hospital physical examination of 50 as the control group to take the research object,spectrophotometric method for the determination of coronary heart disease patients and control subjects serum PON1 arylesterase activity,PON1 arylesterase activity at the same time with statistics the different degree of coronary heart disease,PON1 arylesterase activity between patients with coronary heart disease and control group comparison study and different severity of coronary heart disease patients,the patients with coronary heart disease PON1 aromatic ester enzyme activity,age,gender,BMI,TC,total cholesterol,low density lipoprotein cholesterol LDL-C and glycerin three greases TG included in the analysis of factors of coronary heart disease multiple linear regression equation,to determine the changes of patients with coronary artery disease by PON1 arylesterase activity,to provide a reference for clinical treatment.Results The activity of PON1 in patients with coronary heart disease was significantly lower than that of the control group,and the difference was statistically significant (P<0.05).Single branch lesions in patients with PON1 arylesterase activity was significantly higher than that of double vessel lesions and three lesions were double branch lesions in patients with PON1 arylesterase activity was significantly higher than that in three patients,the differences were statistically significant (P<0.05).According to the multiple linear regression analysis showed that coronary heart disease and the patient′s age,gender,BMI,TC,LDL-C,TG and PON1 arylesterase activity (P<0.05),which was related with age,gender,BMI,TC,LDL-C and TG were positively correlated,negatively correlated with PON1 arylesterase activity.Conclusion The PON1 activity of in patients with coronary heart disease is significantly decreased,and the extent of the disease is more severe,the more obvious the decline of PON1,the activity of PON1 shows a negative correlation with coronary heart disease.
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Objective To explore the correlations of vascular endothelial growth factor (VEGF) and paraoxonase 1 (PON1) gene polymorphism with diabetic retinopathy. Methods A total of 168 patients with diabetes mellitus(DM) in the Second People's Hospital of Xining City were selected from January 2013 to December 2015, and were divided into the DM group (48 cases), proliferative diabetic retinopathy (PDR) group (66 cases) and non-proliferative diabetic retinopathy (NPDR) group (54 cases). A total of 104 healthy subjects were selected as the control group (NC group). The VEGF and PON1 gene polymorphisms were detected by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), and levels of superoxide dismutase (SOD) and malondialdehyde (MDA) of all subjects were detected by using UV spectrophotometer. Results Compared with the NC group, the systolic blood pressures and glycated hemoglobin levels in the DM group, NPDR group and PDR group were significantly increased,there were statistically significant differences (P<0.05). No statistically significant difference was found in diastolic blood pressure and levels of cholesterol,triglyceride, high density lipoprotein among these groups (P>0.05). There was statistically significant difference in systolic blood pressure between PDR group and NPDR group (P< 0. 05), while no statistically significant difference was found in diastolic blood pressure and levels of cholesterol, triglyceride,high density lipoprotein and glycated hemoglobin between the two groups (P>0.05). The incidence rate of DR in the patients with CC,CT and TT genotype was 71.05%, 56.27 % and 38.64 %, respectively. The incidence rate of DR in the patients with CCgenotype was significantly higher than that in the patients with CT or TT genotype (P< 0.05). No statistically significant difference was found in SOD and MDA levels of healthy subjects with different PON1 192 genotypes (P>0.05). The SOD level of DR patients with QQ genotype was lower than that of patients with QR or RR genotype,and the MDA level of DR patients with QQ genotype was higher than that of patients with QR or RR genotype,the difference was statistically significant (P<0.05). Conclusion The expression of VEGF and PON1 genes could affect the development and progression of DR. PON1 gene might control the progression of DR by affecting the expression of oxidative kinase in DR patients.
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High-density lipoprotein ( HDL) is negatively related to the risk of cardiovascular diseases such as atherosclerosis .Recent studies have shown that HDL activates a variety of target cells , such as vascular endothelial cells and macrophages , and activates the related cell signaling pathway to exert an anti-atherosclerosis role .HDL is a complex substance which composes of multiple particles .The changes of many factors affect the characteristics and functions of HDL, and then affect the activation of endothelial nitric oxide synthase ( eNOS) .This paper summarizes the recent correla-tion studies, and expounds the related factors that affect the HDL-eNOS signaling pathway .