Paraoxonase 1 gene (Gln192–Arg) polymorphism and the risk of coronary artery disease in type 2 diabetes mellitus

Many studies have examined the associations between paraoxonase‐1 (PON1) genetic polymorphisms (Q192R, rs662 and L55M, rs854560) and the susceptibility to type 2 diabetes mellitus (T2DM) across different ethnic populations. However, the evidence for the associations remains inconclusive. In this study, we performed a meta‐analysis to clarify the association of the two PON1 variants with T2DM risk. We carried out a systematic search of PubMed, Embase, CNKI and Wanfang databases for studies published before June 2017. The pooled odds ratios (ORs) for the association and their corresponding 95% confidence intervals (CIs) were calculated by a random‐ or fixed‐effect model. A total of 50 eligible studies, including 34 and 16 studies were identified for the PON1 Q192R (rs662) and L55M (rs854560) polymorphism, respectively. As for the PON1 Q192R polymorphism, the 192R allele was a susceptible factor of T2DM in the South or East Asian population (OR > 1, P < 0.05) but represented a protective factor of T2DM in European population (OR = 0.66, 95% CI = 0.45–0.98) under a heterozygous genetic model. With regard to the PON1 L55M polymorphism, significant protective effects of the 55M allele on T2DM under the heterozygous (OR = 0.77, 95% CI = 0.61–0.97) and dominant (OR = 0.80, 95% CI = 0.65–0.99) genetic models were found in the European population, while no significant associations in the Asian populations under all genetic models (P > 0.05). In summary, by a comprehensive meta‐analysis, our results firmly indicated that distinct effects of PON1 genetic polymorphisms existed in the risk of T2DM across different ethnic backgrounds.

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“…For example, the study of Elnoamany et al . included 40 control subjects and the MAF of PON1 Q192R was 0.213, while the study of Gokcen et al . .…”

Section: Discussionmentioning

confidence: 99%

“…One of the reasons may be the small number of subjects in the control group. For example, the study of Elnoamany et al [45] included 40 control subjects and the MAF of PON1 Q192R was 0.213, while the study of Gokcen et al [47]. included 30 control subjects and the MAF of PON1 Q192R was 0.5.…”

Section: Discussionmentioning

confidence: 99%

European versus Asian differences for the associations between paraoxonase‐1 genetic polymorphisms and susceptibility to type 2 diabetes mellitus

Luo

Ren

Liu

et al. 2018

J Cellular Molecular Medi

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“…Among these factors, DM, which is characterized by increased oxidative stress [2], ranks as the major risk factor for the development of coronary artery disease (CAD) despite current treatments for DM [3]. Moreover, methods to assess CAD risk adequately in asymptomatic individuals are not yet available [4].…”

Section: Introductionmentioning

confidence: 99%

“…Additionally, given the role of hyperglycemia in inducing oxidative stress directly by depleting natural anti-oxidants and facilitating the production of reactive oxygen species, the protective effects of PON1 activity against peroxidation of LDL particles has been speculated to be more important in type 2 diabetic patients than in non-diabetic subjects [3]. …”

Section: Introductionmentioning

confidence: 99%

Relation of Paraoxonase 1 Activity with Biochemical Variables, Brachial Artery Intima-Media Thickness in Patients with Diabetes with or without Obesity

Karakaya

Özdemir²,

Mert³

et al. 2018

Obes Facts

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Aim: The sodium-sparing effect of insulin leads to increase in total sodium pool of the body which is a chronic stimulus for atrial natriuretic peptide (ANP). In our study we aimed to determine the relationship between ANP and microvascular complications of diabetes. Methods: 60 patients, 30-70 years old, with the diagnosis of type 2 diabetes mellitus (DM) are enrolled into the study. Patients with a chronic disease other than DM are excluded. Blood samples for routine biochemical tests are taken after at least 12 h fasting at 8-9 am. Blood samples for glucose and insulin levels are taken 2 h after a standard meal. Blood tubes with EDTA are used for ANP levels. The microvascular complications of the patients are evaluated. Results: 32 of the patients had microvascular complications. Age, BMI, waist and hip circumferences, and ANP levels were significantly higher in the group with microvascular complications. There were no significant differences in waist-to-hip ratio, blood glucose, HbA1c, fasting insulin, postprandial insulin, fasting HOMA, postprandial HOMA as well as sodium, potassium, magnesium, calcium and lipid levels between the two groups. When the relationship between ANP and obesity, retinopathy, neuropathy, nephropathy, diabetes time, HbA1c, or sex are evaluated separately, the only significant parameters related to ANP were obesity and retinopathy. Conclusion: In our study we have found that there was a significant relationship between ANP levels and microvascular complications of diabetes. Future studies are needed to show if ANP is the stimulus of microvascular complication development/progression or only an epiphenomenon.

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“…Type 2 diabetes mellitus (T2DM) is a component of metabolic syndrome associated with dyslipidaemia, hypertension, impaired fibrinolysis, and increased pro-coagulation factors. [1][2][3] It ranks as the major risk factor for the development of coronary artery disease (CAD) 4,5 due to the central role of oxidative stress in the pathology of diabetes mellitus. 6,7 In addition to cardiovascular manifestations, diabetes mellitus has been associated with an increased risk of micro-and macrovascular complications, which are a major cause of morbidity and mortality, 8 as oxidative stress is considered a link between diabetes mellitus and related complications.…”

Section: Introductionmentioning

confidence: 99%

Relationship between MPV and paraoxonase-1 activity, brachial artery diameter and IMT in patients with diabetes mellitus

Karakaya

Okuturlar

Mert

et al. 2016

Journal of Endocrinology, Metabolism and Diabetes of South Afri

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Higher mean platelet volume (MPV) in diabetic patients has been considered as an emerging risk factor for diabetes related micro-and macrovascular complications. Human paraoxonase 1/arylesterase (PON1), which has antioxidant and antiatherogenic properties, is documented in high oxidative stress conditions like uncontrolled diabetes. The present study aimed to evaluate the relationship between mean platelet volume (MPV) and paraoxonase-1 (PON-1) activity, brachial artery diameter (BAd) and intima media thickness (BA-IMT), in diabetic patients with regard to obesity and diabetic complications. Methods: Two-hundred and one diabetic patients (mean age: 52.4 ± 13.4 years, 73.6% females) were grouped according to obesity and diabetic complications (microvascular and macrovascular). Data on demographics, anthropometrics, diabetic complications, MPV levels, BAd and BA-IMT, and serum paraoxonase and arylesterase activities were recorded. The correlation of MPV values to paraoxonase and arylesterase activities, BAd and BA-IMT was evaluated. Results: Paraoxonase and arylesterase values were 119.8 ± 37.5 U/L and 149.0 ± 39.9 U/L, respectively, with no significant difference in respect of obesity and macrovascular complications. Significantly lower values for paraoxonase (107.5 ± 30.7 vs. 123.9 ± 38.8 U/L, p = 0.007) and arylesterase (132.1 ± 30.2 vs. 154.7 ± 41.2, U/L, p = 0.001) were noted in patients with microvascular complications. MPV values were 9.10 ± 0.87 fL, with no significant difference across the groups and no significant correlation with other parameters. Conclusion: In conclusion, PON-1 activity is more significantly decreased in diabetic patients with microvascular than macrovascular complications with no effects on MPV values. On the other hand, no relationship was found between thrombogenic activity and PON-1 activity, BAd and BA-IMT regardless of obesity and diabetic complications.

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Paraoxonase 1 gene (Gln192–Arg) polymorphism and the risk of coronary artery disease in type 2 diabetes mellitus

Cited by 7 publications

References 37 publications

European versus Asian differences for the associations between paraoxonase‐1 genetic polymorphisms and susceptibility to type 2 diabetes mellitus

European versus Asian differences for the associations between paraoxonase‐1 genetic polymorphisms and susceptibility to type 2 diabetes mellitus

Relation of Paraoxonase 1 Activity with Biochemical Variables, Brachial Artery Intima-Media Thickness in Patients with Diabetes with or without Obesity

Relationship between MPV and paraoxonase-1 activity, brachial artery diameter and IMT in patients with diabetes mellitus

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