Paraoxonase (PON)-1: a brief overview on genetics, structure, polymorphisms and clinical relevance

Shunmoogam, Nelusha; Naidoo, Poobalan; Chilton, Robert

doi:10.2147/vhrm.s165173

Cited by 122 publications

(105 citation statements)

References 48 publications

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“…Apart from its antioxidant effects, PON1 has multiple implications in metabolic disorders due to the fact of its promiscuous multiple activities. The enzyme was recently named a "regulator of glucose and lipid homeostasis" [37] which exerts its implication on the pathogenesis of NAFLD/NASH due to the fact of its protective function against oxidative stress and inflammation [37,38].…”

Section: Discussionmentioning

confidence: 99%

Paraoxonase-1 Serum Concentration and PON1 Gene Polymorphisms: Relationship with Non-Alcoholic Fatty Liver Disease

Milaciu

Vesa

Bocşan

et al. 2019

JCM

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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. Author Contributions: Conceptualization, M.V.M., L.C., I.C.B. and M.A.; methodology, M.V.M., L.C., M.A., and S , .C.V.; validation, M.A., L.C., D.M.M., V.N., D.S. and S.P.; formal analysis, S , .C.V.; investigation, M.V.M., L.C., R.M.P., I.C.B. and S.P.; resources, I.C.B., S , .C.V., R.M.P., D.M.M., A.D.B. and A.L.R.; writing-original draft preparation, M.V.M.; writing-review and editing, S , .C.V., L.C., I.C.B. and M.A.; visualization, A.L.R.; supervision,

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Section: Discussionmentioning

confidence: 99%

Paraoxonase-1 Serum Concentration and PON1 Gene Polymorphisms: Relationship with Non-Alcoholic Fatty Liver Disease

Milaciu

Vesa

Bocşan

et al. 2019

JCM

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“…A recently published meta‐analysis showed association of reduced PON1 activity with DM and development of chronic DM complications . Some studies failed to see changes in PON1 levels in diabetics compared with controls, but without a doubt, PON1activity in diabetics was lower . Reduced PON1 activity in diabetics is worthy of further research due to several reasons.…”

Section: Pon1 and Diseases Connected With Atherosclerosis Developmentmentioning

confidence: 99%

“…75 Some studies failed to see changes in PON1 levels in diabetics compared with controls, but without a doubt, PON1activity in diabetics was lower. 76 Reduced PON1 activity in diabetics is worthy of further research due to several reasons. One of them is nonenzymatic enzyme glycation as a consequence of hyperglycemia.…”

Section: Pon 1 and Diabetes Mellitusmentioning

confidence: 99%

Paraoxonase 1 and atherosclerosis‐related diseases

et al. 2019

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A direct and an indirect relationship between paraoxonase 1 (PON1) and atherosclerosis exists. Given PON1's physical location within high‐density lipoprotein (HDL) particles and its recognized enzyme activity, it is certainly reasonable to suggest that PON1 facilitates the antiatherogenic nature of HDL particles. PON1 also plays a role in regulating reverse cholesterol transport, antioxidative, anti‐inflammatory, antiapoptotic, vasodilative, and antithrombotic activities and several endothelial cell functions. HDL dysfunctionality is a more recent issue and seems to be centered on pathological conditions affecting HDL structure and size profiles. This review is focused on the role of PON1 status in different atherosclerosis‐related diseases that we have studied over the last twenty years (coronary heart disease, acute ischemic stroke, diabetes mellitus type 2, end‐stage renal disease, chronic obstructive pulmonary disease, and sarcoidosis) with the aim to determine the true value of PON1 as a biomarker. The role of PON1 in cancer is also covered, as risk factors and mechanisms underlying both atherosclerosis and cancer share common features.

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“…Human paraoxonase1 is a calcium-dependent hydrolytic enzyme and it is speculated that plays an important role in diseases such as diabetes and atherosclerosis. Low PON1 activity is associated with higher risk of cardiovascular diseases (Shunmoogam et al, 2018). PON1 is implicated in hydrolytic detoxification of many OPIs and is known for hydrolyzing paraoxon, phenyl acetate and 4-nitrophenyl acetate as well as lactones (Costa et al, 2005;Ceron et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

“…While as many as 8 SNPs are known to occur in PON1, important ones are at positions 55 (Leu-Met) and 192 (Gln-Arg). These polymorphisms could either affect substrate specificity or biological activity of PON1 (Humbert et al, 1993;Yamuda et al, 2001;Shunmoogam et al, 2018). PON1 is known for protecting LDL particles from oxidation, a property of PON1 that is majorly responsible for its cardioprotective effects (Mackness et al, 1993;Mackness et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Plasma paraoxonase1 activity in rats treated with monocrotophos: a study of the effect of duration of exposure

Nagaraju

Joshi

Vamadeva

et al. 2019

Interdisciplinary Toxicology

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We have earlier demonstrated the potential of monocrotophos (MCP), a highly toxic organophosphorus insecticide (OPI), to elicit insulin resistance in rats after chronic exposure. Given the understanding of role of paraoxonase1 (PON1) in OPI toxicity and diabetes pathology, this study was envisaged to understand the effect of duration of exposure to MCP on plasma PON1 activity in rats. Rats were administered MCP per os at 1/20 and 1/10th LD50 as daily doses for 180 days. Interim blood samples were collected at 15, 30, 45, 90 and 180 d for analysis of plasma parameters. Exposure to MCP for 45 resulted in persistent trend of hyperinsulinemia, while significant increase in fasting glucose levels was observed after 180 days. MCP caused suppression of plasma cholinesterase activity though the study period, albeit extent of inhibition was more severe during the early phase of the study. Exposure to MCP for 180 d resulted in hypertriglyceridemia and marginal decrease in HDL-C levels. MCP failed to modulate PON1 activity in plasma during the early phase of the study (up to 45 d). However, prolonged exposure resulted in significant increase in the plasma PON1 activity. This suggests that manifestation of insulin resistance in rats subjected to chronic exposure to MCP is associated with increase in PON1 activity. Our work provides rationale for studying whether the increase in PON1 activity observed in the present study serves to counter the deleterious effect of long term exposure to organophosphorus insecticides on metabolic homeostasis.

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Paraoxonase (PON)-1: a brief overview on genetics, structure, polymorphisms and clinical relevance

Cited by 122 publications

References 48 publications

Paraoxonase-1 Serum Concentration and PON1 Gene Polymorphisms: Relationship with Non-Alcoholic Fatty Liver Disease

Paraoxonase-1 Serum Concentration and PON1 Gene Polymorphisms: Relationship with Non-Alcoholic Fatty Liver Disease

Paraoxonase 1 and atherosclerosis‐related diseases

Plasma paraoxonase1 activity in rats treated with monocrotophos: a study of the effect of duration of exposure

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