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 The association between PON1 gene polymorphisms (Q192R and L55M) and nephrotic syndrome in Iraqi children

2021 ◽  
Vol 2 (03) ◽  
pp. 118-130
Author(s):  
Raghad Ali ◽  
Rayah Baban ◽  
Shatha Ali
Keyword(s):  
Nephrotic Syndrome ◽  
Lipid Profile ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Paraoxonase 1 ◽  
Pon1 Activity ◽  
Healthy Controls ◽  
Coding Region ◽  
Pon1 Gene ◽  
Homozygous Genotype

Background: The role of paraoxonase 1 enzyme (PON1) and its single nucleotide polymorphisms (SNPs) in children with nephrotic syndrome (NS) has been reported previously in different ethnic and racial groups with divergent results. The human PON1 gene contains two coding region polymorphisms leading to two different PON1 isoforms. Objectives: The aim of the present study was to find out the association between the PON1 (Q192R and L55M) polymorphisms and their relation with serum PON1 activity as well as lipid profile tests (total cholesterol, TC; triglycerides, TG; high-density lipoprotein cholesterol, HDL-c; and low-density lipoprotein cholesterol, LDL-c) in children with NS. Methods: This study included a total of 80 participants (40 with NS in the age group of 2-14 years and 40 age and sex-matched healthy controls). The PON1 enzyme activity and lipid profile tests were measured in serum samples of all included participants. The PON1 genotype was determined by PCR-restriction enzyme fragment length polymorphism (PCR-RFLP) for both PON1 alleles (192 and 55) SNPs. Results: Our findings showed that the mean levels of lipid profile tests (TC, TG, LDL-c) were significantly increased in patients when compared with healthy controls (p<0.05), while the HDL-c concentration was significantly decreased in patients than that of controls. Also, the patients had significantly lower concentrations of PON1 when compared with the controls regardless of the genotype Q192R and L55M polymorphisms. Moreover, the homozygous RR genotype for PON1 SNP 192 and MM homozygous genotype for PON1 SNP 55 were significantly frequent in patients when compared with the controls. Conclusions: Our results support that the presence of the homozygous RR genotype for PON1 SNP 192 and MM homozygous genotype for PON1 SNP 55 were significantly higher in patients compared with the controls.

Association of PON1 gene polymorphisms and enzymatic activity with risk of coronary artery disease

2021 ◽  
Vol 17 (1) ◽  
pp. 119-126
Author(s):  
Charuta Godbole ◽  
Saket Thaker ◽  
Prafulla Kerkar ◽  
Milind Nadkar ◽  
Nithya Gogtay ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Enzymatic Activity ◽  
Gene Polymorphisms ◽  
Pon1 Activity ◽  
Pon1 Gene ◽  
Artery Disease ◽  
Pon1 Polymorphisms ◽  
Serum Pon1 Activity ◽  
Control Study

Background: The present case–control study evaluated the association of PON1 gene polymorphisms and enzyme activity in the western Indian population. Materials & methods: Angiographically proven coronary artery disease (CAD) formed the cases. PON1 polymorphisms (Q192R, L55M) and enzymatic activity (paraoxonase) were assessed. Results: A total of 502 participants (251 per group) were studied. PON1 Q192R and L55M polymorphisms were not associated with the risk of CAD. Notably, a weak association was observed between Q192R polymorphisms and the risk of CAD. CAD patients had significantly lower PON1 enzymatic activity (U/L) as compared with the controls regardless of the genotype. Conclusion: Low serum PON1 activity was confirmed to be an independent predictor for the risk of CAD.

scholarly journals The effect of paraoxonase 1 (PON1) gene polymorphisms T(-107)C and L55M and diet composition on serum PON1 activity in women

2021 ◽  
Author(s):  
Bianka Machado Zanini ◽  
Leticia Burkert ◽  
Fabiola Goettem dos Santos ◽  
Michal M. Masternak ◽  
José Augusto Crespo-Ribeiro ◽  
...  
Keyword(s):  
Gene Polymorphisms ◽  
Diet Composition ◽  
Paraoxonase 1 ◽  
Pon1 Activity ◽  
Pon1 Gene ◽  
Serum Pon1 Activity

scholarly journals Paraoxonase 1 Activity, Polymorphism and Atherosclerosis Risk Factors in Patients Undergoing Coronary Artery Surgery

2019 ◽  
Vol 8 (4) ◽  
pp. 441 ◽  
Author(s):  
Anna Wysocka ◽  
Marek Cybulski ◽  
Andrzej P.Wysokiński ◽  
Henryk Berbeć ◽  
Janusz Stążka ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Risk Factors ◽  
Coronary Heart Disease ◽  
Heart Disease ◽  
Family History ◽  
Paraoxonase 1 ◽  
High Density Lipoproteins ◽  
Pon1 Activity ◽  
Diabetic Patients ◽  
Paraoxonase Activity

Background: Paraoxonase1 (PON1), an enzyme connected to high density lipoproteins (HDL) particles, plays an important role in protecting arteries against atherosclerosis. The serum activity and concentration of PON1 depends on several genetic polymorphisms as well as environmental factors. Materials and methods: Investigated population consisted of 71 patients aged 43–76 years with confirmed coronary heart disease (CHD). Established risk factors of CHD such as hypertension, elevated total cholesterol and LDL cholesterol (LDL-C), low HDL cholesterol (HDL-C), diabetes mellitus, obesity, smoking and premature CHD in family history were assessed. PON1 genotype for –108C/T promotor region was determined by polymerase chain reaction-restriction fragments length polymorphism (PCR–RFLP) method. Paraoxonase activity towards paraoxon and arylesterase activity towards phenyl acetate were measured spectrophotometrically. Results: Significant correlations between diabetes mellitus and paraoxonase activity (R = –0.264, p = 0.026) and between the premature coronary heart disease in family history and PON1 activity (R = –0.293, p = 0.013) were found. In multivariate analysis, PON1 paraoxonase activity was independently of confounding factors associated with diabetes (OR = 0.985; p = 0.024) and premature CHD in family history (OR = 0.983; p = 0.027). PON1 activity towards aryl acetate positively correlated with HDL-C level (R = 0.255, p = 0.032). In patients treated with statins, PON1 paraoxonase activity was significantly (p = 0.033) higher than in patients without treatment. Conclusions: In diabetic patients with CHD, paraoxonase activity is lower than in normoglycemic patients despite similar lipid profiles. Diabetes and positive family history in patients with overt CHD are associated with the serum PON1 activity, which might be an additional factor helpful in evaluating cardiovascular risk in this group of patients.

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.

PON1 gene polymorphisms in patients with chronic obstructive pulmonary disease

2018 ◽  
Vol 71 (11) ◽  
pp. 963-970
Author(s):  
Marija Grdić Rajković ◽  
Sanja Popović-Grle ◽  
Andrea Vukić Dugac ◽  
Dunja Rogić ◽  
Ivana Rako ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Operating Characteristic ◽  
Fragment Length Polymorphism ◽  
Characteristic Curve ◽  
Paraoxonase 1 ◽  
Pon1 Activity ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Pon1 Gene

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 the frequencies of Q192R, L55M and −108C>T polymorphisms and association of those polymorphisms with paraoxonase and arylesterase activities in patients with COPD.MethodsPON1 genotype was determined by PCR–restriction fragment length polymorphism method. PON1 activity was measured by paraoxon and phenylacetate.ResultsOnly −108C>T polymorphism resulted in significantly different distribution of genotypes and alleles, with higher frequency of TT genotype and T allele in patients compared with control subjects. Moreover, T allele (OR 2.29 (95% CI 1.54 to 3.41); p<0.001) as well as TT genotype (OR 5.00 (95% CI 2.19 to 11.43); p<0.001) showed an association with the disease. −108C>T polymorphism was suggested as a significant diagnostic predictor for the disease (OR (95% CI) 2.65 (1.53 to 4.59), p=0.001), with an area under the receiver operating characteristic curve of 0.90 (95% CI 0.84 to 0.93) and with 83.90% of correctly classified cases.ConclusionsHigher frequency of TT genotype and T allele could contribute to the observed reduction of PON1 activity in patients with COPD. T allele and TT genotype are associated with COPD, and the PON1−108C>T polymorphism could be a potential predictor of the disease.

scholarly journals Sex Difference Impacts on the Relationship between Paraoxonase-1 (PON1) and Type 2 Diabetes

Antioxidants ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 683
Author(s):  
Valentina Rosta ◽  
Alessandro Trentini ◽  
Angelina Passaro ◽  
Giovanni Zuliani ◽  
Juana Maria Sanz ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Cardiovascular Complications ◽  
Serum Glucose ◽  
Paraoxonase 1 ◽  
High Density Lipoproteins ◽  
Pon1 Activity ◽  
Partial Loss ◽  
The Relationship ◽  
Gender Specific

Type-2 diabetes (T2D) and its cardiovascular complications are related to sex. Increasing evidence suggests that paraoxonase 1 (PON1) activity, an antioxidant enzyme bound to high-density lipoproteins (HDL), is implicated in the onset and clinical progression of T2D. Since we previously showed that PON1 is a sexual dimorphic protein, we now investigated whether sex might impact the relationship between PON1 and this chronic disease. To address this aim, we assessed PON1 activity in the sera of 778 patients, including controls (women, n = 383; men, n = 198) and diabetics (women, n = 79; men = 118). PON1 activity decreased in both women and men with T2D compared with controls (p < 0.05 and p > 0.001, respectively), but the change was 50% larger in the female cohort. In line with this result, the enzyme activity was associated with serum glucose level only in women (r = −0.160, p = 0.002). Notably, only within this gender category, lower PON1 activity was independently associated with increased odds of being diabetic (odds ratio (95% Confidence interval: 2.162 (1.075–5.678)). In conclusion, our study suggests that PON1-deficiency in T2D is a gender-specific phenomenon, with women being more affected than men. This could contribute to the partial loss of female cardiovascular advantage associated with T2D.

scholarly journals Accuracy and Biological Variation of Human Serum Paraoxonase 1 Activity and Polymorphism (Q192R) by Kinetic Enzyme Assay

2007 ◽  
Vol 53 (2) ◽  
pp. 310-317 ◽  
Author(s):  
Richard W Browne ◽  
Stephen T Koury ◽  
Susan Marion ◽  
Gregory Wilding ◽  
Paola Muti ◽  
...  
Keyword(s):  
Genetic Polymorphisms ◽  
Disease Risk ◽  
Pcr Amplification ◽  
Automated Analysis ◽  
Epidemiological Studies ◽  
Paraoxonase 1 ◽  
Pon1 Activity ◽  
Restriction Enzyme Digestion ◽  
Enzyme Preparations ◽  
Genotype Assignment

Abstract Background: Paraoxonase 1 (PON1) phenotype is a better predictor of atherosclerosis risk than are PON1 genetic polymorphisms alone. Larger studies are required to determine the role of PON1 and there is a need for standardized PON1 assays between laboratories. Methods: We have adapted 5 enzyme kinetic assays for high-throughput automated analysis of PON1 activity. Using different substrates and reaction conditions, we measured PON1 activity and used activity ratios to identify the PON1 Q192R genetic polymorphisms and assessed the accuracy of the genotype assignments in 79 adult study participants by comparing them with genotypes determined by AlwI restriction enzyme digestion of a 176-bp PCR amplification product from genomic DNA. Imprecision was determined using pooled serum and purified enzyme preparations. Biological variability was estimated by analysis of serial samples from 17 individuals. Variability parameters were compared with total cholesterol as a point of reference to a recognized biomarker of coronary heart disease risk. Results: Salt stimulation and inhibition ratios were 97.4% and 94.7% correct in assigning Q192R genotype, respectively. Analytical imprecision (CV) was 1.0%–3.0% for phenylacetate and paraoxon substrate assays and 3.0%–8.0% for the para-nitrophenylacetate substrate assays. Combination of the 2 ratios into a double ratio resulted in 100% correct genotype classification. Conclusion: The described methods for measurement of PON1 activity and accurate genotype assignment are rapid and have potential to facilitate the efficient investigation of PON1 status in clinical and epidemiological studies.

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