Paraoxonase Gene Polymorphisms Research Articles

The Effects of PON1 (Q192R, rs662) Gene Polymorphism, Heavy metals and Oxidative Stress on Risk of Recurrent Spontaneous Abortion in Samples of Iraqi Women

Recurrent spontaneous abortion (RSA) is defined as the occurrence of two or more spontaneous pregnancy losses before reaching the midpoint of gestation. Oxidative stress plays a pivotal role in the pathogenesis of RSA, serving as a key factor in its underlying causes. This research aims to investigate the connection between the Q192R polymorphisms identified in the PON1 gene, responsible for encoding an antioxidant enzyme and the vulnerability to RSA. Paraoxonase 1 (PON1) is a critical enzyme in the body's antioxidant defence system, safeguarding cells against damage caused by reactive oxygen species and heavy metal concentrations that affect pregnancy. The most prevalent PON1 polymorphism is Q192R (rs662), known to influence the antioxidant activity and power of the PON1 enzyme. In this research, blood samples were collected from two groups: 50 women with RSA and 50 women who were apparently in good health. Following DNA extraction, high-resolution melting (HRM) analysis was used to identify the studied SNP; Elisa was used to determine DNA damage and MDA concentrations in serum and heavy metals were determined by a Graphite Furnace-Atomic Absorption Spectrophotometer (GFAAS). The results of this study showed significantly higher levels of 8-OHdG, MDA, arsenic and lead in serum in RSA patients than in apparently healthy women. The genotype findings indicated that the prevalence of the QR (AG) genotype in women experiencing recurrent spontaneous abortion was notably greater than that in seemingly healthy women (74% compared to 16%, respectively, with an odds ratio of 27.2). The values of allele frequency for the A allele were 0.76 and 0.51 for apparently healthy women and women with recurrent spontaneous abortion respectively. The G allele frequency was 0.24 and 0.49 for apparently healthy women and women with recurrent spontaneous abortion respectively. The heterozygous QR genotype is related to the risk of RSA and the minor allele (G allele) is increased in women with RSA.

Association of paraoxonase-1 (Q192R) gene polymorphism with coronary artery spasm during cardiac catheterisation in Egyptians

Background Coronary artery spasm is among the etiology of myocardial infarction. Oxidative stress is involved in the pathogenesis of coronary artery spasm (CAS). Paraoxonase-1 (PON1) is an HDL-bound antioxidant enzyme that protects LDL from oxidative modification. Oxidative-stress-related genetic factors and certain polymorphisms in the paraoxonase 1 gene might influence the pathogenesis of CAS. We aimed to investigate the association between PON1 gene polymorphism and its enzymatic activity and coronary artery spasm during cardiac catheterization. Methods and results The study population was 150 patients who underwent elective coronary angiography. Subjects were genotyped to the Q192R polymorphism (rs662) on the PON1 gene by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), and PON1 activity was quantitatively analyzed by enzyme linked immunosorbent assay. Results showed that the subjects carrying the RR genotype and R allele were significantly more likely to develop coronary artery spasm (OR=4.2, 2.03, P< 0.006, P˂0.02, respectively). Moreover, serum PON1 levels were significantly decreased (P˂0.001) in the CAS group. RR genotype of PON1 Q192R polymorphism, Tc, LDLc, TG, catheter size, and paroxonase-1 serum level are independent predictors of coronary spasm. Conclusion We conclude that the PON1 (rs662) gene polymorphism is associated with CAS during cardiac catheterization in Egyptians. The PON1-192R allele and lower serum enzyme concentration may play an important role in coronary spasm.

PON1, APOE and SDF-1 Gene Polymorphisms and Risk of Retinal Vein Occlusion: A Case-Control Study.

Numerous studies have tried to evaluate the potential role of thrombophilia-related genes in retinal vein occlusion (RVO); however, there is limited research on genes related to different pathophysiological mechanisms involved in RVO. In view of the strong contribution of oxidative stress and inflammation to the pathogenesis of RVO, the purpose of the present study was to investigate the association of inflammation- and oxidative-stress-related polymorphisms from three different genes [apolipoprotein E (APOE), paraoxonase 1 (PON1) and stromal cell-derived factor 1 (SDF-1)] and the risk of RVO in a Greek population. Participants in this case-control study were 50 RVO patients (RVO group) and 50 healthy volunteers (control group). Blood samples were collected on EDTA tubes and genomic DNA was extracted. Genotyping of rs854560 (L55M) and rs662 (Q192R) for the PON1 gene, rs429358 and rs7412 for the APOE gene and rs1801157 [SDF1-3'G(801)A] for SDF-1 gene was performed using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Multiple genetic models (codominant, dominant, recessive, overdominant and log-additive) and haplotype analyses were performed using the SNPStats web tool to assess the correlation between the genetic polymorphisms and the risk of RVO. Binary logistic regression analysis was used for the association analysis between APOE gene variants and RVO. Given the multifactorial nature of the disease, our statistical analysis was adjusted for the most important systemic risk factors (age, hypertension and diabetes mellitus). The dominant genetic model for the PON1 Q192R single nucleotide polymorphism (SNP) of the association analysis revealed that there was a statistically significant difference between the RVO group and the control group. Specifically, after adjusting for age and hypertension, the PON1 192 R allele (QR + RR) was found to be associated with a statistically significantly higher risk of RVO compared to the QQ genotype (OR = 2.51; 95% CI = 1.02-6.14, p = 0.04). The statistically significant results were maintained after including diabetes in the multivariate model in addition to age and hypertension (OR = 2.83; 95% CI = 1.01-7.97, p = 0.042). No statistically significant association was revealed between the other studied polymorphisms and the risk of RVO. Haplotype analysis for PON1 SNPs, L55M and Q192R, revealed no statistically significant correlation. In conclusion, PON1 192 R allele carriers (QR + RR) were associated with a statistically significantly increased risk of RVO compared to the QQ homozygotes. These findings suggest that the R allele of the PON1 Q192R is likely to play a role as a risk factor for retinal vein occlusion.

Association between Q192R Polymorphism of Paraoxonase-1 Gene and Risk of Coronary Artery Disease: A Case-control Study

Introduction: Coronary Artery Disease (CAD) is a complex metabolic disorder in which lifestyle and genetic factors are known to play key roles in pathogenesis. Extensive studies have examined the role of Paraoxonase 1 (PON1) polymorphisms as genetic markers of CAD. However, the evidence regarding their role in the aetiology of CAD remains contradictory. Aim: The aim of this study was to determine the genotypic/ allelic frequency of the Q192R polymorphism of the PON1 gene and its association with the risk of CAD. Materials and Methods: A case-control study was conducted at the Department of Biochemistry in collaboration with the Department of Medicine, Sri Guru Ram Das Institute of Medical Sciences and Research, Amritsar, Punjab, India, from November 2019 to December 2022. A total of 100 participants were divided into two groups: group I (CAD patients) and group II (healthy controls) to investigate the association between the Q192R polymorphism and CAD risk. The genotypic and allelic frequencies of the Q192R polymorphism of the PON1 gene and its association with CAD were determined using Polymerase Chain Reaction and Restriction Fragment Length Polymorphism (PCR-RFLP), followed by 2% agarose gel electrophoresis. The data were statistically analysed using the Chi-square test. Results: There were a total of 50 participants in each group (29 males and 21 females), with a mean age of 47.02±8.79 years in group I and 37.70±7.29 years in group II (p-value&lt;0.001). The present study confirmed that individuals with QR+RR genotype compared to QQ genotype (OR: 2.47; 95% CI: 1.10-5.55; p-value=0.03) of the Q192R polymorphism were associated with an increased risk of CAD. A higher frequency of the RR genotype of the Q192R polymorphism was detected in CAD patients, and it was associated with a 3-fold increased risk of developing CAD (p-value&lt;0.05). However, the difference between QR versus QQ genotypes {Odds Ratio (OR): 2.13; 95% CI: 0.89-5.12, p-value=0.09} was found to be statistically insignificant. Furthermore, a significantly higher frequency of the R allele was observed in CAD patients compared to controls (OR 2.12, 95% CI: 1.18-3.84, p-value=0.01). Conclusion: In conclusion, the Q192R polymorphism of the PON1 gene was associated with an increased risk of CAD in the Punjabi population. The results confirmed that the presence of the R allele was associated with an increased risk of CAD.

Paraoxonase gene polymorphisms: Understanding the biochemical and genetic basis of coronary artery disease

ObjectivesSerum paraoxonase (PON) is a glycoprotein with antioxidant and anti-atherosclerotic activities. The Q192R and L55M gene polymorphisms of PON have been implicated as risk factors for coronary artery disease (CAD) but have not been extensively explored in South Indians. We aimed to assess the Q192R and L55M genetic polymorphisms of the PON1 gene in participants with CAD, including genotypes and allele frequencies for PON1 gene polymorphism. MethodsThis prospective case-control study involved 20 participants in each group. Patients with angiographically demonstrated CAD were included in the case group. PON1 activity was measured, and PON gene polymorphism was determined. Serum PON was quantitatively analyzed with a RayBio® Human PON1 ELISA kit. Chi square tests were used to assess the association of the genotypes with sex and any comorbidities in cases and controls. A p value ≤ 0.05 was considered significant. ResultsMutant type L55M polymorphism was observed in 50% of patients, whereas wild type Q192R polymorphism was observed in 42.5% of the participants. The mean PON values between groups did not significantly differ, whereas PON U/L was significantly (p = 0.001) lower in the case group. The L55M polymorphism did not significantly differ between the case and the control groups (p = 0.213), whereas the Q192R polymorphism was statistically significant in cases compared with controls (p ≤ 0.001) ConclusionLow plasma PON1 and HDL levels, and higher LDL, total cholesterol and triglyceride levels were observed in patients with CAD. More patients with CAD than healthy individuals had Q192R polymorphism.

The effect of Paraoxonase gene polymorphisms and paraoxonase enzyme activity on Non-Hodgkin lymphoma

Non-Hodgkin Lymphoma (NHL) is a malignant lymphoproliferative disease. Antioxidant paraoxonase enzyme (PON1) has a vital role in the elimination of potential carcinogenic organophosphate molecules. The polymorphisms in the PON1 gene, especially Q192R and L55M, may affect negatively the activity and synthesis of PON1 enzyme. The aim of this study was to evaluate the effect of these polymorphisms together with PON1 enzyme activity on NHL. We surveyed these polymorphisms together with PON1 enzyme activity in 93 patients with NHL and in 93 healthy individuals by real-time polymerase chain reaction (RT-PCR) and spectrophotometer. Although carrying the M and R alleles of L55M and Q192R polymorphisms increases the risk of NHL, they were not significant. Furthermore, the NHL patients carrying 192 R allele had significantly lower enzyme activity than controls having same allele (P = 0.025). This research is the first study worldwide investigating the effect of Q192R and L55M polymorphisms on PON1 enzyme activity in NHL disease. The risk of developing NHL may be further increased in individuals with low enzyme activity having R risk allele of the Q192R polymorphism. The present study suggests that these polymorphisms in NHL disease should be analyzed together with PON1 enzyme activity in larger populations. Supplemental data for this article is available online at https://doi.org/10.1080/15257770.2022.2052315 .

Paraoxonase 1: Could it be important for asthma in children?

Objective: The paraoxonase 1 (PON-1) enzyme is an important antioxidant. The balance between oxidative stress and antioxidant defense mechanisms is disturbed during asthma attacks. The activity of the PON-1 enzyme is related to PON-1 gene polymorphism. This study aimed to evaluate the activity of PON-1 enzyme and Q192R polymorphism in asthmatic children. Material and methods: During the 2013-2014 period, we performed a prospective study with 34 asthmatic (study group) and 34 healthy (control group) children. Serum PON-1 activity was evaluated in the study group at the onset of an asthma attack and at the end, and also in the control group. Q192R gene polymorphism of asthmatic children, which is known to affect the PON-1 enzyme activity was also investigated. Results: There was no significant difference in terms of serum PON-1 enzyme activity and PON-1 gene polymorphism between the asthmatic children and healthy controls. However, a significant increase was observed at the PON-1 enzyme activity of asthmatic children at the end of the asthma attack compared to its onset. Conclusion: The PON-1 enzyme activity and Q192R genetic polymorphism in asthmatic children are not different from those of healthy children, but PON-1 enzyme activity is higher at the end of an asthma attack compared to the onset. PON-1 enzyme, as a member of the antioxidant mechanism, may be important both in understanding the pathophysiology of asthma and in the development of new medications for asthma.

PON1 (Paraoxonase 1) Q192R Gene Polymorphism in Ischemic Stroke among North Indian Population.

Background:PON1 is an High Density Lipoprotein (HDL)-associated esterase. Two common polymorphisms in the PON1 gene, Q192R and L55M substitutions, determine the inter-individual variation in PON1 activity. The association of these polymorphisms with the risk of ischemic stroke remains controversial. In the present study, the role of PON1 Q192R gene polymorphism in ischemic stroke was studied in the Indian population.Design and Methods:In the present case-control study, the PON1 Q192R gene polymorphism was screened in ischemic stroke patients (n: 63) and age, sex-matched controls (n: 63) using thePolymerase Chain Reaction-Restriction Segment Length Polymorphism (PCR-RFLP) method.Results:The mean age of stroke presentation was 58.11 ± 15.4 years. A total of 17.4% cases presented with young stroke (<45 years age) and 9.52% cases were seen to have a recurrent stroke. The distribution of -192Q/R PON1 gene polymorphism was not seen to differ between cases and controls. The traditional stroke risk factors did not have any effect on the PON1 genotype expression. A multivariate logistic regression analysis was done in order to assess an independent association of age, gender, traditional stroke risk factors, and PON1 polymorphism with acute ischemic stroke. However, neither the RR genotype nor the presence of the R allele was associated with an increase in the risk of acute ischemic stroke (OR [RR genotype]-4.76, P value: 0.24, 95% CI: 0.3497–64.8531; OR [R allele]-0.94, P value: 0.90, 95% CI: 0.3516–2.4989).Conclusion:PON1 Q192R gene polymorphism is not associated with an increased risk of acute ischemic stroke in the North Indian population. Further studies with a larger sample size are needed before PON1 Q192R gene polymorphism can be considered as a genetic risk factor for ischemic stroke.

Association SOD2 and PON1 Gene Polymorphisms with Polycystic Ovary Syndrome in Saudi Women

Polycystic ovary syndrome (PCOS) is a considered one of the most common female disorders associated with reproductive, metabolic, and psychological problems. The etiology of PCOS is still not yet disclosed; however, evidence for a genetic basis has been reported. In this study, we investigate the associations between superoxide dismutase 2 (SOD2) (rs4880) and paraoxonase 1 (PON1) (rs705379) polymorphisms in PCOS in Saudi women. The study included 99 females with PCOS and 98 healthy women as a control. Single nucleotide polymorphisms (SNPs) of promoter regions were determined using TaqMan genotyping assays. Regarding the polymorphism at SOD2 (rs4880), the CC, CT, and TT genotypes were present at rates of 32, 61, and 7% in PCOS patients, and 47, 43, and 10% in controls, respectively. The frequency of the CT genotype in PCOS patients (0.61) was significantly higher than in controls (0.43) (OR = 2.05, CI: 1.16–3.61; p = 0.015). The wild homozygous genotype (CC) with the phenotype alanine appears to confer protection against the disease compared to molecules sharing at least one valine (genotypes, CT + TT). Regarding the polymorphism at PON1 (rs705379), the rates of CC, CT, and TT genotypes were 34, 50, and 16% in PCOS patients and 33, 63, and 2% in controls, respectively. The rate of the TT genotype in PCOS patients was significantly higher than that in controls (p = 0.0058). SOD2 and PON1 polymorphisms may be genetic factors that affect the occurrence of PCOS in Saudi females.

Paraoxonase 1 concerning dyslipidaemia, cardiovascular diseases, and mortality in haemodialysis patients

Paraoxonase 1 (PON1) is known for preventing atherosclerosis through lipid-modifying features, antioxidant activity, anti-inflammatory, anti-apoptosis, anti-thrombosis, and anti-adhesion properties. Uremic patients requiring haemodialysis (HD) are especially prone to atherosclerosis and its complications. We analysed the PON1 gene (PON1) polymorphisms and serum PON1 (paraoxonase) activity concerning dyslipidaemia and related cardiovascular diseases and mortality to show how they associate under uremic conditions modified by maintenance HD treatment. The rs662 AA + AG (OR 1.76, 95%CI 1.10–2.80, P = 0.018), rs854560 TT (OR 1.48, 95%CI 1.04–2.11, P = 0.031), and rs854560 AT + TT (OR 1.28, 95%CI 1.01–1.63, P = 0.040) contributed to the prevalence of atherogenic dyslipidaemia diagnosed by the triglyceride (TG)/HDL-cholesterol ratio ≥ 3.8. The normalized serum PON1 activity positively correlated with atherogenic dyslipidaemia (ẞ 0.67 ± 0.25, P = 0.008). The PON1 rs854560 allele T was involved in the higher prevalence of ischemic cerebral stroke (OR 1.38, 1.02–1.85, P = 0.034). The PON1 rs705379 TT genotype contributed to cardiovascular (HR 1.27, 95% CI 1.03–1.57, P = 0.025) and cardiac (HR 1.34, 95% CI 1.05–1.71, P = 0.018) mortality. All P-values were obtained in multiple regression analyses, including clinical variables. Multifaceted associations of PON1 with dyslipidaemia, ischemic cerebral stroke, and cardiovascular mortality in HD patients provide arguments for the consideration of PON1 and its protein product as therapeutic targets in the prevention of atherosclerosis and its complications in uremic patients.

Influence of Human Paraoxonase-1 Polymorphism (Q192R) on Serum Levels of Clinical Biomarkers Indicatives of Cardiovascular Diseases Risk in Mexican Women.

Human paraoxonase-1 (PON1) is a hydrolytic enzyme related in the onset, establishment, and progression of inflammatory illnesses, including cardiovascular diseases (CVD). Therefore, the primary goal of this investigation was to determinate the influence of the PON1 gene polymorphism (Q192R) on prognostic biomarkers of CVD in women (n = 350) from San Luis Potosi, Mexico. For everyone enrolled, anthropometric, clinical, and biochemical measurements were acquired. Q192R polymorphism of the PON1 gene was assessed by real-time PCR using TaqMan probes. Also, quantification and/or calculation of suggested predictive CVD biomarkers were completed. The association between PON1(Q192R) polymorphism with clinical predictive CVD biomarkers was assessed using univariate and multivariate logistic regression models. Genotype PON1 (Q192R) frequencies were: 18%, 47% and 35% for QQ, QR, and RR, respectively. Besides, the frequency of the variant R allele was 0.58. Furthermore, robust significant associations were found between PON1 (Q192R) polymorphism with serum ADMA [OR (95% CI); 3.50 (1.20-5.00), p < 0.01]; FABP4 [2.50 (2.15-3.95), p < 0.01]; and miR-126 [1.50 (1.15-2.00), p < 0.01] levels after adjusting for probable confounders. Data found in this research strongly support the notion that proposes a crucial role of PON1 enzyme (Q192R polymorphism) as a genetic determinant in the CVD risk in Mexican women.

Association of SRB1 and PON1 gene polymorphisms with type 2 diabetes mellitus: a case control study

Single-nucleotide polymorphism (SNP) in Paraoxonase 1 (PON1) and scavenger receptor class b member 1 (SRB1) gene has been associated with impairing high-density lipoprotein (HDL) functionality as an antioxidant and shown to diminish ability of PON1 in cholesterol homeostasis. Several studies found that SRB1 and PON1 polymorphism increases T2DM risk. Our study aimed to investigate the association and susceptibility of polymorphic variants in SRB1 rs9919713 and PON1 rs662 with type 2 diabetes mellitus. In the present case-control study, 250 type 2 diabetes mellitus patients (T2DM) and 250 healthy volunteer were recruited. The genotypes of PON1 and SRB1 were determined by using polymerase chain reaction-restriction fragment length polymorphism (RFLP-PCR) technique, and biochemical analysis was done using standard protocol. C and R alleles showed significant association with T2DM susceptibility with an odds ratio of 1.42 (p < 0.005) and 1.40 (p < 0.007), respectively. The frequency of CC and RR genotype was significantly higher in T2DM patients compared with healthy controls. Furthermore, CC and RR genotypes were significantly associated with higher LDL and low HDL levels. Additionally, no other significant association was observed. We conclude that the PON1 and SRB1 gene polymorphisms may probably surrogate biomarkers for T2DM susceptibility.

Q192R variant in paraoxonase 1 gene confers susceptibility to leiomyoma.

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. 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. Genotyping was performed using tetra-primer amplification refractory mutation system-polymerase chain reaction. Chi-square test was selected to evaluate differences between the groups. 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). 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.

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.

The most effective polymorphisms of paraoxonase-1 gene on enzyme activity and concentration of paraoxonase-1 protein in type 2 diabetes mellitus patients and non-diabetic individuals: A systematic review and meta-analysis

IntroductionMany studies have evaluated the association of paraoxonase-1 (PON1) gene polymorphisms with enzyme activity and concentration in type 2 diabetes mellitus (T2DM). However, the exact impact of these polymorphisms is not still obvious. Hence, we conducted a systematic review and meta-analysis to clarify the association of PON1 polymorphisms with its enzyme characteristics in T2DM patients and non-diabetic individuals. MethodsWe searched electronic databases including PubMed, Web of Science, Embase and Scopus for publications by April 2018. The pooled response ratio (rr) for the association and their corresponding 95% confidence intervals (CIs) were calculated using a fixed-effect model. ResultsFifteen relevant studies fulfilled our inclusion criteria. The results showed a 1.25-fold increase in total PON1 activity in non-diabetic group against T2DM patients (p-value = 0.024). Also, only Q192R and L55M polymorphisms had sufficient studies to be included in the meta-analysis. All three genotypes of Q192R polymorphism showed significantly different activities between the study groups with the highest pooled effect size for RR genotype (rrQQ < rrQR < rrRR) while this difference was seen only in LL genotype of L55M polymorphism. Therefore, Q192R polymorphism was more correlated with type 2 diabetes mellitus. In case of concentration, there was no significant differences between two groups (p-value = 0.897). ConclusionCurrent meta-analysis suggested that the observed difference of total PON1 activity was due to the different activity of various genotypes of PON1 enzyme in case of L55M and Q192R polymorphisms so that LL and RR genotypes had the most important role in the establishment of mentioned difference.

Research Article Human Serum Paraoxonase (PON-1) and hemochromatosis gene (HFE) gene polymorphisms in occupationally exposed lead workers from Saudi Arabia

Research Article Human Serum Paraoxonase (PON-1) and hemochromatosis gene (HFE) gene polymorphisms in occupationally exposed lead workers from Saudi Arabia

PON1 gene polymorphisms in patients with chronic obstructive pulmonary disease

AimsChronic obstructive pulmonary disease (COPD) is characterised with oxidative stress. Paraoxonase 1 (PON1) is an enzyme, coded by PON1 gene, with distinctive antiatherogenic and antioxidative roles. We aimed to investigate...

Association of PON1 gene polymorphisms with polycystic ovarian syndrome risk: a meta-analysis of case-control studies.

Evidences showed that paraoxonase 1 (PON1) gene polymorphism has an impact on women's susceptibility to polycystic ovarian syndrome (PCOS) by influencing the expression and activity of PON1. However, the effects of three PON1 polymorphisms (- 108 C>T, L55M and Q192R) on the incidence of PCOS have generated inconsistent results. Here, we conducted a meta-analysis to investigate the association between PON1 polymorphisms and PCOS risk. All eligible trials were identified via systematic searches of multiple literature databases. Outcome data were synthesized by using crude odds ratio with 95% confidence interval. Heterogeneity was assessed with the I2 test. Publication bias and subgroup analyses were also performed. A total of 2449 cases and 1977 controls from nine studies were selected for analysis. The pooled results showed a significant association between PCOS risk and PON1 - 108 C/T polymorphism in the following genetic models [allelic, 0.72 (0.56-0.92); homozygote, 0.51 (0.32-0.82); heterozygote, 0.44 (0.25-0.78); and dominant 0.47 (0.29-0.77)]. For the PON1 192 Q/R polymorphism, a significant relationship was found in the allelic model [0.62 (0.41-0.93)] and recessive model [0.61 (0.37-0.98)]. PCOS risk was also linked to PON1 L55M polymorphism in the heterozygote model [0.62 (0.39-0.98)] and dominant model [0.63 (0.41-0.96)]. Our study has shown that PON1 - 108 C/T polymorphism might be associated with increased risk of PCOS under the allelic, homozygote, heterozygote, and dominant models. Additionally, PON1 192 Q/R and L55M polymorphisms were significantly related only in the allelic and recessive model, and in the heterozygote and dominant model, respectively.

Genotype-phenotype Analysis of Paraoxonase 1 in Schizophrenic Patients Treated with Atypical Antipsychotics.

ObjectiveRecent studies suggest a possible involvement of low paraoxonase 1 (PON1) enzyme activities in the association between schizophrenia, treatment with atypical antipsychotics and increased cardiovascular (CVD) risk. In the present study, we aimed at investigating the PON1 status in a group of schizophrenic patients treated with either olanzapine or other antipsychotic, as compared to a group of healthy control participants.MethodsWe assessed the arylesterase (AREase) and paraoxonase (POase) activities of PON1, as well as three common polymorphisms of PON1 gene (Q192R, L55M, −108C>T).ResultsWe found significantly lower (−13.3%) AREase activity in schizophrenic patients, along with significantly lower (−18.2%) POase activity in olanzapine-treated patients with QQ genotype. Furthermore, we found a significant difference between groups in L55M polymorphism distribution, whereas Q192R and −108C>T polymorphisms distributions were similar.ConclusionWe identified the olanzapine-treated patients with QQ genotype as having the lowest PON1 (POase) activity, providing a possible way of identifying schizophrenic patients exposed to the greatest risk of CVD.

Association of paraoxonase-1 gene polymorphisms with insulin resistance in South Indian population

Background and aimInsulin resistance plays a crucial role in the pathogenesis of type 2 diabetes and cardiovascular diseases. Recently, paraoxonase-1(PON1) is reported to have an ability to reduce insulin resistance by promoting glucose transporter-4 (GLUT-4) expression in vitro. Single nucleotide polymorphism (SNP) in PON1 is associated with variability in enzyme activity and concentration. Based on this we aimed to investigate the association of PON1 (Q192R and L55M) polymorphisms with the risk of developing insulin resistance in adult South Indian population. MethodsTwo hundred and eighty seven (287) Type 2 diabetes patients and 293 healthy controls were enrolled in this study. All the study subjects were genotyped for PON1 (Q192R and L55M) missense polymorphisms using polymerase chain reaction-restriction fragment length polymorphism (PCRRFLP) method. Fasting serum insulin level was measured by ELISA. ResultsThe distribution of QR/RR and LM/MM genotypes were significantly higher in type 2 diabetes patients compared with healthy controls. Moreover, the R and M alleles were significantly associated with type 2 diabetes with an Odds Ratio of 1.68 (P < 0.005) and 2.24 (P < 0.005) respectively. SNP 192 Q > R genotypes were found to be significantly associated with higher BMI, cholesterol, triglycerides, LDL, fasting serum insulin and HOMA-IR. Further, the mutant allele or genotypes of PON1 L55M were associated with higher BMI, triglycerides, VLDL, fasting serum insulin and HOMA-IR among adult type 2 diabetes patients. ConclusionPON1 (Q192R and L55M) polymorphisms may play a crucial role in pathogenesis and susceptibility of insulin resistance thus leads to the development of type 2 diabetes in South Indian population.