Associations between paraoxonase 1 (PON1) polymorphisms and susceptibility and PON1 activity in rheumatoid arthritis patients, and comparison of PON1 activity in patients and controls: a meta-analysis

2019 ◽  
Vol 38 (8) ◽  
pp. 2141-2149 ◽  
Author(s):  
Sang-Cheol Bae ◽  
Young Ho Lee
Keyword(s):  
Rheumatoid Arthritis ◽  
Meta Analysis ◽  
Paraoxonase 1 ◽  
Pon1 Activity ◽  
Pon1 Polymorphisms

scholarly journals Paraoxonase 1 and Chronic Obstructive Pulmonary Disease: A Meta-Analysis

Antioxidants ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1891
Author(s):  
Jun Watanabe ◽  
Kazuhiko Kotani ◽  
Alejandro Gugliucci
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Meta Analysis ◽  
Paraoxonase 1 ◽  
Pon1 Activity ◽  
Chronic Obstructive ◽  
Healthy Controls ◽  
Obstructive Pulmonary Disease ◽  
Paraoxonase Activity ◽  
Severe Copd

Oxidative stress is a driving factor in the pathophysiology of chronic obstructive pulmonary disease (COPD). While paraoxonase 1 (PON1) is an antioxidant enzyme and a potential biomarker of this disease, data regarding the status of PON-1 in COPD are inconclusive. In this regard, to shed light on this issue, we performed a meta-analysis of data on PON1 activity in COPD. Electronic databases (MEDLINE, Embase and CENTRAL) were searched for available studies on PON1 activity in patients with stable COPD published before October 2021. A meta-analysis was performed using random-effects models. Twelve studies (12 studies on paraoxonase and three on arylesterase) were identified. Patients with COPD had lower levels of paraoxonase activity (standard mean difference [SMD] −0.77, 95% confidence interval [CI] −1.35 to −0.18) and arylesterase activity (SMD −1.15, 95% CI −1.95 to −0.36) in comparison to healthy controls. In subgroup analyses, paraoxonase activity was lower in patients of studies as consisted of mainly non-severe COPD (SMD −1.42, 95% CI −2.04 to −0.79) and, by contrast, slightly higher in patients of studies including severe COPD (SMD 0.33, 95% CI 0.02 to 0.64) in comparison to healthy controls. Arylesterase activity showed a similar trend. Overall, PON1 activity was lower in patients with COPD, suggesting that PON1-related antioxidant defense is impaired in COPD. Future studies are warranted.

scholarly journals Paraoxonase 1 Phenotype and Protein N-Homocysteinylation in Patients with Rheumatoid Arthritis: Implications for Cardiovascular Disease

Antioxidants ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 899
Author(s):  
Jolanta Parada-Turska ◽  
Grażyna Wójcicka ◽  
Jerzy Beltowski
Keyword(s):  
Rheumatoid Arthritis ◽  
Protein Concentration ◽  
Serum Proteins ◽  
Density Lipoprotein ◽  
Cardiovascular Complications ◽  
Paraoxonase 1 ◽  
Pon1 Activity ◽  
Phenyl Acetate ◽  
Control Subjects ◽  
Increased Risk

Paraoxonase 1 (PON1) is the high density lipoprotein-associated esterase which inhibits the development of atherosclerosis by metabolizing lipid peroxidation products as well as hydrolyzing proatherogenic metabolite of homocysteine (Hcy), Hcy thiolactone, which otherwise reacts with lysine groups of proteins, thus forming N-Hcy-protein in a process referred to as protein N-homocysteinylation. Rheumatoid arthritis (RA) is the chronic inflammatory autoimmune disease associated with increased risk of cardiovascular complications, but the underlying mechanisms are incompletely understood. We examined PON1 status and N-homocysteinylation of serum proteins in patients with RA. Blood was collected from 74 RA patients and 70 control subjects. PON1 activity was measured toward synthetic (paraoxon, phenyl acetate) and natural (Hcy thiolactone) substrates. PON1 protein concentration was measured by ELISA. Total Hcy as well as N-Hcy-protein were measured in serum as well. PON1 activity toward Hcy thiolactone was lower in RA patients than in control subjects which was accompanied by increased concentration of N-Hcy-protein despite normal total Hcy concentration. PON1 protein concentration was unchanged in the RA group, but the specific enzyme activity was reduced. When RA patients were categorized according to the DAS28-ESR score, PON1 concentration and enzymatic activity were lower whereas N-Hcy-protein was higher in those with high disease activity. PON1 activity and Hcy thiolactone were correlated with DAS28-ESR score and myeloperoxidase concentration. In conclusion, RA is associated with deficiency of PON1 activity and increased protein N-homocyseinylation which may contribute to accelerated development of cardiovascular diseases.

Evaluation of Association Between Q192R and L55M Genetic Polymorphisms of PON1 and Serum Paraoxonase-1 Activity in Healthy Individuals, a Meta-Analysis

2018 ◽  
Vol 25 (2) ◽  
pp. 171-180 ◽  
Author(s):  
Mostafa Saadat
Keyword(s):  
Meta Analysis ◽  
Activity Level ◽  
Paraoxonase 1 ◽  
Coding Region ◽  
Paraoxonase Activity ◽  
Variant Alleles ◽  
Pon1 Polymorphisms ◽  
Serum Paraoxonase ◽  
The Relationship ◽  
Healthy Participants

Abstract Background and Aims: Several studies have reported the alteration of the paraoxonase 1 (PON1) enzyme activity in various diseases, including diabetes mellitus. The Q192R and L55M are two genetic variations in the coding region of PON1. To evaluate the relationship between these polymorphisms and the alteration in serum paraoxonase activity, the present meta-analysis was carried out. Material and Methods: Eligible studies published before October 2017 was identified in several databases. The paraoxonase activity in subjects with variant alleles of the study polymorphisms were normalized using the activity of the QQ or LL genotypes. The pooled mean effect of alterations in activity level and its 95% confidence intervals (95% CI) was calculated. Results: Thirty-two studies including 11532 healthy participants were used for the present meta-analysis. The paraoxonase activity was increased in the QR and RR genotypes. This elevation was greater among Caucasians than those among Asians and Africans. The activity in the LM and MM genotypes compared with the LL genotype were decreased, this reduction in Caucasians was greater than Africans. Conclusions: At least in part other PON1 polymorphisms and environmental factors may accounts for heterogeneity between studies.

scholarly journals Investigation of paraoxonase 1 activity of the workers at the plant, who have long-term contact with organophosphorus compounds

2017 ◽  
Vol 15 (1) ◽  
pp. 57
Author(s):  
Natalia D Razgildina ◽  
Valentina V Miroshnikova ◽  
Aleksey V Fomichev ◽  
Ekaterina V Malisheva ◽  
Alexandra A Panteleeva ◽  
...  
Keyword(s):  
Enzymatic Activity ◽  
Organophosphorus Compounds ◽  
Paraoxonase 1 ◽  
Pon1 Activity ◽  
Control Group ◽  
Pon1 Gene ◽  
Polymorphic Variants ◽  
Pon1 Polymorphisms ◽  
Serum Pon1 Activity

Background. Liver enzyme paraoxonase 1 (PON1) plays an important role in protection the organism from toxic effects of organophosphorus compounds (OPs) via their hydrolysis whose rate and efficiency depend on PON1 serum level activity. PON1 activity is largely determined by the polymorphic variants of the PON1 gene. Effect of long-term work with exposure to the toxic OPs on the PON1 activity is almost unknown. The aim of the present work was to study the effect of long-term work with exposure to the toxic OPs on PON1 serum enzymatic activity depending on polymorphisms Q191R, L54M, C(-108)T PON1 gene. Materials and methods. PON1 serum enzymatic activity and PON1 polymorphisms were determined in men, who were categorized in 2 groups: workers of companies providing storage and disposal of the OPs (68) and control group (37). The PON1 191, PON1 55 and PON1 108 polymorphisms were studied by polymerase chain reaction/restriction fragment length polymorphism. PON1 serum enzymatic activity was measured by a spectrophotometric method using paraoxon. Results. PON1 activity in workers with exposure to the toxic OPs relative was increased compared to the control group (p = 0,027). Differences in serum PON1 activity was shown for the carriers of certain genotypes of the PON1 gene: PON1 serum activity was higher in workers compared to controls only for LL genotype (L54M polymorphism) and C allele (C(-108)T polymorphism) carriers (p < 0,001 and p = 0,002, correspondently). Conclusion. We suggest that the increase in serum PON1 activity in workers providing storage and disposal of OPs could be modulated with the polymorphic variants of the PON1 gene.

scholarly journals Paraoxonase 1 gene polymorphisms and enzyme activities in diabetes mellitus

2008 ◽  
pp. 717-726
Author(s):  
M Flekač ◽  
J Škrha ◽  
K Žídková ◽  
Z Lacinová ◽  
J Hilgertová
Keyword(s):  
Gene Polymorphisms ◽  
Diabetes Control ◽  
Paraoxonase 1 ◽  
High Density Lipoproteins ◽  
Pon1 Activity ◽  
Diabetic Patients ◽  
Restriction Enzyme Digestion ◽  
Coding Region ◽  
Pon1 Gene ◽  
Pon1 Polymorphisms

Paraoxonase 1 (PON1), an antioxidant enzyme closely associated with HDL (high-density lipoproteins), preserves LDL (low-density lipoproteins) against oxidation. Less protection may be therefore supposed by decreased PON1 activity. This study was undertaken to investigate the association of PON1 gene polymorphisms with diabetic angiopathy and to evaluate the relationship of these polymorphisms with PON1 activity. Total of 86 Type 1 (T1DM) and 246 Type 2 (T2DM) diabetic patients together with 110 healthy subjects were examined. DNA isolated from leukocytes was amplified with polymerase chain reaction (PCR) followed by restriction enzyme digestion. The products were analyzed for L55M and Q192R polymorphisms in coding region and for –107 C/T and –907 G/C in promotor sequence of PON1. Serum enzyme activity was measured spectrophotometrically. Significant differences were found between T1DM or T2DM and control persons in L55M polymorphism (allele M more frequent in T1DM and T2DM vs. controls, p<0.05) and Q192R polymorphism (R allele less frequent in T1DM and T2DM vs. controls, p<0.01) of the PON1 gene. Serum PON1 activity was significantly decreased in T1DM (110±68 nmol/ml/min) and T2DM patients (118±69 nmol/ml/min) compared to the control persons (203±58 nmol/ml/min), both p<0.01. The presence of MM and QQ genotypes was accompanied by lower PON1 activity than of LL and RR genotypes (p<0.05), respectively. Better diabetes control was found in patients with LL than with MM genotypes and similarly in RR genotype than QQ genotype with p<0.05. Significantly different allele frequencies were found in diabetic patients with macroangiopathy than in those without it (M: 0.59 vs. 0.44. R: 0.12 vs. 0.19, p<0.01). The association of PON1 polymorphisms, lower PON1 activity and poorer diabetes control found in patients with macroangiopathy further support the idea of genetic factors contributing to the development of vascular disorders in diabetes.

scholarly journals Why Should Psychiatrists and Neuroscientists Worry about Paraoxonase 1?

2019 ◽  
Vol 17 (11) ◽  
pp. 1004-1020 ◽  
Author(s):  
Estefania Gastaldello Moreira ◽  
Karine Maria Boll ◽  
Dalmo Guilherme Correia ◽  
Janaina Favaro Soares ◽  
Camila Rigobello ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Drug Targets ◽  
Paraoxonase 1 ◽  
Pon1 Activity ◽  
Psychiatric Diseases ◽  
Physically Active ◽  
Effective Strategies ◽  
Q192r Polymorphism ◽  
Pubmed Database ◽  
Pon1 Polymorphisms

Background: Nitro-oxidative stress (NOS) has been implicated in the pathophysiology of psychiatric disorders. The activity of the polymorphic antioxidant enzyme paraoxonase 1 (PON1) is altered in diseases where NOS is involved. PON1 activity may be estimated using different substrates some of which are influenced by PON1 polymorphisms. Objectives: 1) to review the association between PON1 activities and psychiatric diseases using a standardized PON1 substrate terminology in order to offer a state-of-the-art review; and 2) to review the efficacy of different strategies (nutrition, drugs, lifestyle) to enhance PON1 activities. Methods: The PubMed database was searched using the terms paraoxonase 1 and psychiatric diseases. Moreover, the database was also searched for clinical trials investigating strategies to enhance PON1 activity. Results: The studies support decreased PON1 activity as determined using phenylacetate (i.e., arylesterase or AREase) as a substrate, in depression, bipolar disorder, generalized anxiety disorder (GAD) and schizophrenia, especially in antipsychotic-free patients. PON1 activity as determined with paraoxon (i.e., POase activity) yields more controversial results, which can be explained by the lack of adjustment for the Q192R polymorphism. The few clinical trials investigating the influence of nutritional, lifestyle and drugs on PON1 activities in the general population suggest that some polyphenols, oleic acid, Mediterranean diet, no smoking, being physically active and statins may be effective strategies that increase PON1 activity. Conclusion: Lowered PON1 activities appear to be a key component in the ongoing NOS processes that accompany affective disorders, GAD and schizophrenia. Treatments increasing attenuated PON1 activity could possibly be new drug targets for treating these disorders.

Paraoxonase-1 and myeloperoxidase correlate with vascular biomarkers in overweight patients with newly diagnosed untreated hyperlipidaemia

VASA ◽  
2017 ◽  
Vol 46 (5) ◽  
pp. 370-376 ◽  
Author(s):  
Anita Szentpéteri ◽  
Noémi Zsíros ◽  
Viktória E. Varga ◽  
Hajnalka Lőrincz ◽  
Mónika Katkó ◽  
...  
Keyword(s):  
Adhesion Molecule ◽  
Oxidized Ldl ◽  
Vascular Complications ◽  
Cd40 Ligand ◽  
Paraoxonase 1 ◽  
Intercellular Adhesion Molecule ◽  
Pon1 Activity ◽  
Intercellular Adhesion Molecule 1 ◽  
Inflammatory Parameters ◽  
Vascular Biomarkers

Abstract. Background: In hyperlipidaemic state, increased levels of myeloperoxidase (MPO) and decreased paraoxonase-1 (PON1) activity have been reported; however, their relationships with other atherosclerotic biomarkers have not been completely clarified. Patients and methods: Serum concentrations of lipid and inflammatory parameters, MPO levels, and PON1 activities were investigated in 167 untreated hyperlipidaemic patients with and without vascular complications and in 32 healthy controls. Additionally, levels of CD40 ligand (sCD40L) and asymmetric dimethyl arginine (ADMA), soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1, and oxidized LDL were determined. Results: We found elevated C-reactive protein (CRP), ADMA, sCD40L, sICAM-1 concentrations, and higher MPO levels in patients with vascular complications compared to those without. The PON1 arylesterase activity correlated negatively with sCD40L, ADMA, and sICAM-1 levels, respectively. In contrast, MPO concentrations showed positive correlations with sCD40L, ADMA, and sICAM-1 levels, respectively. Conclusions: It can therefore be stated that PON1 activity and MPO level correlate strongly with the vascular biomarkers, highlighting the importance of the HDL-associated pro- and antioxidant enzymes in the development of endothelial dysfunction and atherogenesis.

‘I’m an expert in me and I know what I can cope with’: Patient expertise in rheumatoid arthritis

2014 ◽  
Vol 10 (3) ◽  
pp. 249-261 ◽  
Author(s):  
Tessa Sanderson ◽  
Jo Angouri
Keyword(s):  
Rheumatoid Arthritis ◽  
Meta Analysis ◽  
Healthcare Systems ◽  
Specific Knowledge ◽  
Active Involvement ◽  
Domain Specific ◽  
Access To Health ◽  
Patient Expertise ◽  
Domain Specific Knowledge ◽  
The Uk

The active involvement of patients in decision-making and the focus on patient expertise in managing chronic illness constitutes a priority in many healthcare systems including the NHS in the UK. With easier access to health information, patients are almost expected to be (or present self) as an ‘expert patient’ (Ziebland 2004). This paper draws on the meta-analysis of interview data collected for identifying treatment outcomes important to patients with rheumatoid arthritis (RA). Taking a discourse approach to identity, the discussion focuses on the resources used in the negotiation and co-construction of expert identities, including domain-specific knowledge, access to institutional resources, and ability to self-manage. The analysis shows that expertise is both projected (institutionally sanctioned) and claimed by the patient (self-defined). We close the paper by highlighting the limitations of our pilot study and suggest avenues for further research.

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