Paraoxonase-1 Is Not Associated with Coronary Artery Calcification in Type 2 Diabetes: Results from the PREDICT Study

Mackness, Bharti; Marsillach, Judit; Elkeles, R. S.; Godsland, Ian F.; Feher, Michael; Rubens, Michael B.; Flather, Marcus; Humphries, Steve E.; Cooper, J. Mark; Mackness, Mike

doi:10.1155/2012/953768

Cited by 12 publications

(8 citation statements)

References 45 publications

(66 reference statements)

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“…Concordant with the atheroprotective role of ArylE activity, several studies have shown low activity to be associated with increased CAD risk, CAD severity, endothelial dysfunction, worse collateral flow, and adverse cardiovascular outcomes . However, in contrast to this, a few other studies showed high activity to be associated with increased CAD severity, coronary calcification, and increased risk of myocardial infarction, while other studies have not shown any such associations …”

Section: Discussionmentioning

confidence: 93%

High‐density lipoprotein‐associated paraoxonase‐1 activity for prediction of adverse outcomes in outpatients with chronic heart failure

Hammadah

Kalogeropoulos

Georgiopoulou

et al. 2017

European J of Heart Fail

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Aims Decreased arylesterase (ArylE) activity of paraoxonase-1, a HDL-associated protein with anti-inflammatory and antioxidant properties, has been associated with increased risk of cardiac events in patients with ischemic heart failure (HF). We aim to investigate the prognostic significance of changes in serum ArylE activity over time. Methods and results We examined the association between baseline and follow up serum ArylE activity and HF outcomes (death, cardiac transplantation or ventricular assist device implantation) in 299 patients with HF enrolled in a prospective cohort study from 1/2008 to 7/2009, with 145 patients have available follow up levels at 1 year. A significant drop in ArylE activity on follow up was defined as a drop of ≥25% vs. baseline levels. Mean baseline and follow up ArylE activity levels were 110.5±29.8µmol/min/ml and 106.2±29.9µmol/min/ml, respectively. After mean follow up of 2.8±1.1 years, low baseline ArylE activity was associated with increased risk of adverse HF events [HR (lowest vs highest tertile)=2.6(95% CI 1.3–5.5), p=0.01] and HF related hospitalization [incidence rate ratio (lowest vs highest tertile)=2.1(95%CI 1.2–4.1), p=0.016], which remained significant after adjustment for age, male, systolic blood pressure, diabetes, creatinine clearance, coronary artery disease, and HDL Cholesterol levels. Patients who had a significant drop in ArylE activity on follow up (≥25% of baseline levels, n=18), had significantly increased risk of HF events [HR=4.9(95%CI 1.6–14.6), p=0.005], even after adjustment for baseline levels of ArylE activity. Conclusions Reduced baseline ArylE activity and decreased levels on follow up are associated with adverse outcomes in stable outpatients with HF.

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Section: Discussionmentioning

confidence: 93%

High‐density lipoprotein‐associated paraoxonase‐1 activity for prediction of adverse outcomes in outpatients with chronic heart failure

Hammadah

Kalogeropoulos

Georgiopoulou

et al. 2017

European J of Heart Fail

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“…Ikeda et al [22] and Mackness et al [23] reported a low PON1 concentration in coronary heart disease patients compared with healthy patients. Also, it has been demonstrated that decreased PON1 activity predicts a higher risk of major adverse cardiac events and that low serum concentrations of PON1 may be an independent predictor of cardiovascular mortality [22–26].…”

Section: Discussionmentioning

confidence: 99%

PON1 concentration and high-density lipoprotein characteristics as cardiovascular biomarkers

González

Ponce-Ruíz

Rojas-García

et al. 2019

Arch Med Sci Atheroscler Dis

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Introduction: Serum paraoxonase 1 (PON1) is now known to be related to cardiovascular diseases (CVD). The aim of this study was to determine the relationship between PON1 concentration and high-density lipoprotein (HDL) subclasses in patients with proven CVD, cardiovascular risk factors but no CVD (CRF), and in healthy controls (control group). Material and methods: A case-control study was carried out with 69 volunteers from the Mexican Institute of Social Security, Mexico. Clinical parameters, lipid profile, PON1 concentration, PON1 activities (AREase and CMPAase), and HDL subclasses were evaluated. Results: Patients with CVD had significantly higher glucose and lower total cholesterol than the control group had (p < 0.01). AREase activity was not different between the control (122.57 ±30.72 U/ml), CRF (115.81 ±32.81 U/ml), and CVD (109.34 ±29.60 U/ml) groups. PON1 concentration was significantly lower in CVD patients than in CRF and control patients (p < 0.001); a positive correlation was observed between AREase activity and PON1 concentration in the CVD group (Rho = 0.58; p < 0.01). Logistic regression analysis showed that the decrease in PON1 level was associated with the CVD group (RRR = 0.20; 95% CI: 0.09-0.45) but not with the CRF group (RRR = 1.29; 95% CI: 0.89-1.90). Significant differences were observed in HDL 2a and HDL 3a concentrations between the control group and CRF and CVD groups (p < 0.05), but not between the CRF and CVD groups. Conclusions: Our data suggest that PON1 status and HDL characteristics could be early biomarkers that predict the potential for developing CVD.

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“…In contrast, in a study on 589 patients (419 Caucasian, 120 South Asian, 50 other) to determine factors which modulate serum PON1 in type 2 diabetes, PON1 activity associated negatively with insulin resistance, triglycerides and 55 M allele; and positively with 192R allele. While PON1 concentration associated negatively with Caucasian ethnicity and duration of diabetes, and positively with 192R allele [ 19 ].…”

Section: Discussionmentioning

confidence: 99%

Paraoxonase-1 gene Q192R and L55M polymorphisms and risk of cardiovascular disease in Egyptian patients with type 2 diabetes mellitus

El-Lebedy

Kafoury

Haleem

et al. 2014

J Diabetes Metab Disord

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BackgroundIncreased oxidative stress or an impaired antioxidant defense mechanism may play a crucial role in the onset and progression of atherosclerosis. Recently, Paraoxonase −1 (PON1) which accounts for most of the antioxidant effect of high density lipoprotein (HDL) cholesterol has been presented as a potential therapeutic agent against atherosclerosis development. Allele frequencies for PON1 gene that influence enzyme concentration as well as activity differ greatly among ethnic groups and data from several studies showed ethnic variations in the interpretation of cardiovascular disease (CVD) associated with PON1 polymorphisms. In this work, we investigated PON1 Q192R and L55M polymorphisms in Egyptian patients with type 2 diabetes mellitus (T2DM) and its association with CVD.MethodsThe study included 184 subjects classified into 3 groups; T2DM, T2DM + CVD, and healthy controls. PON1 polymorphisms were genotyped by real-time PCR and PON1 concentration was assayed in serum by ELISA (enzyme linked immunesorbent assay).ResultsGenotype and allele frequencies of Q192R were significantly different between controls and diabetic patients. Frequency of QQ genotype was significantly higher in healthy controls, while QR and RR genotypes were significantly higher in diabetic patients (p = 0.02). Frequency of 55LL and LM genotypes were significantly higher in patients than in controls (p = 0.009). Q192R polymorphism associated with CVD in our diabetic patients (p = 0.01) and with low serum PON1 concentration (p = 0.04). Multiple logistic regression analysis revealed significant correlations between 192R and other independent CVD risk factors.ConclusionPON1 192R and 55 L alleles are associated with T2DM. Q192R polymorphism is associated with CVD and lower serum enzyme concentration and might represents a novel risk factor for CVD in Egyptian patients with T2DM.

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Paraoxonase-1 Is Not Associated with Coronary Artery Calcification in Type 2 Diabetes: Results from the PREDICT Study

Cited by 12 publications

References 45 publications

High‐density lipoprotein‐associated paraoxonase‐1 activity for prediction of adverse outcomes in outpatients with chronic heart failure

High‐density lipoprotein‐associated paraoxonase‐1 activity for prediction of adverse outcomes in outpatients with chronic heart failure

PON1 concentration and high-density lipoprotein characteristics as cardiovascular biomarkers

Paraoxonase-1 gene Q192R and L55M polymorphisms and risk of cardiovascular disease in Egyptian patients with type 2 diabetes mellitus

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