Publications (17)41.35 Total impact
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Article: Effect of Astaxanthin Supplementation on Paraoxonase 1 Activities and Oxidative Stress Status in Young Soccer Players.
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ABSTRACT: The purpose of the study was to examine the effects of astaxanthin (Asx) on paraoxonase (PON1) activities and oxidative stress status in soccer players. Forty soccer players were randomly assigned in a double-blind fashion to Asx and placebo (P) group. Blood samples were obtained before, 45 and 90 days after supplementation. PON1 activity was assessed by using two substrates: paraoxon and diazoxon. The oxidative stress biomarkers were also examined: total sulphydryl group content (-SH groups), thiobarbituric acid-reactive substances (TBARS), advanced oxidation protein products and redox balance. The significant interaction effect of supplementation and training (p < 0.05) on PON1 activity toward paraoxon was observed. The PON1 activity toward diazoxon increased in Asx group after 90 days (p < 0.01), while there was no significant difference in P group. SH groups content rose from pre- to post-supplementation period only in Asx group (supplementation and training, p < 0.05; training, p < 0.01). TBARS levels decreased after 45 days and increased after 90 days of regular soccer training in both groups (training, p < 0.001). Redox balance decreased significantly in response to the regular training, regardless of treatment group (training, p < 0.001). Asx supplementation might increase total SH groups content and improve PON1 activity through protection of free thiol groups against oxidative modification. Copyright © 2012 John Wiley & Sons, Ltd.Phytotherapy Research 11/2012; · 2.09 Impact Factor -
Article: A hazardous link between malnutrition, inflammation and oxidative stress in renal patients.
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ABSTRACT: Atherosclerosis is the main cause of mortality in end stage renal disease (ESRD) patients. Malnutrition, inflammation and diminished paraoxonase activity were used to calculate the sum of risk factors for atherosclerosis development in a cohort of 141 chronic renal disease patients. Kaplan-Meier survival analysis was implemented to assess risk of death. Kaplan-Meier analysis (Log rank=12.06, P=0.0072) showed higher risk of death with increasing number of risk factors in haemodialysis patients. Malnutrition in combination with inflammation and oxidative stress is associated with higher mortality in patients on long-term haemodialysis.Clinical biochemistry 05/2012; 45(15):1202-5. · 2.02 Impact Factor -
Article: Changes in LDL and HDL Subclasses in Normal Pregnancy and Associations with Birth Weight, Birth Length and Head Circumference.
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ABSTRACT: Pregnancy is associated with alterations in low-density lipoprotein (LDL) and high-density lipoprotein (HDL) subclasses, but the exact pattern of these variations remains controversial. This study investigates longitudinal changes of plasma LDL and HDL particles distributions during the course of normal pregnancy, as well as associations of maternal LDL and HDL subclasses distributions before delivery with parameters of newborn size. Blood samples were collected from 41 healthy pregnant women throughout entire pregnancy, before delivery and 7 weeks postpartum. LDL and HDL subclasses were determined by gradient gel electrophoresis, while other biochemical parameters were measured by standard laboratory methods. During gestation LDL size significantly decreased (P < 0.001), due to reduction in relative proportion of LDL I (P < 0.01) and increase of LDL II (P < 0.001) and IIIA (P < 0.05) subclasses. In the same time, HDL size and proportions of HDL 2a particles significantly decreased (P < 0.001), with concomitant increase of HDL 3b and 3c subclasses (P < 0.05). Observed alterations were associated with changes in serum triglyceride levels. Rearrangement in LDL subclasses distribution during gestation was transient, while postpartum HDL subclasses distribution remained shifted toward smaller particles. Higher proportion of LDL IVB in maternal plasma before delivery was an independent predictor of smaller birth weights and lengths, while higher proportions of LDL IVB and HDL 2a subclasses were independent determinants of newborns' smaller head circumferences. Routine gestational and prenatal care in otherwise normal pregnancy could be complemented with evaluation of LDL and HDL particles distribution in order to ensure an adequate size of the newborn.Maternal and Child Health Journal 04/2012; · 2.24 Impact Factor -
Article: Longitudinal changes in PON1 activities, PON1 phenotype distribution and oxidative status throughout normal pregnancy.
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ABSTRACT: The purpose of the present study was to determine changes in plasma paraoxonase-1 activity (an indicator of paraoxonase phenotype) throughout normal pregnancy and its relationship with maternal oxidative stress status. The frequencies of the paraoxonase-1 phenotype in the studied population were determined using a two-substrate (paraoxon/diazoxon) activity method. As a parameter of oxidative stress status we measured the redox balance. Paraoxonase-1 activity significantly decreased at gestational week 32. In addition, the lipid profile was more atherogenic. Redox balance was significantly increased across gestational weeks. There were independent direct associations between maternal smoking habits before pregnancy, glucose concentrations and redox balance with PON1 activity in the third trimester. This study shows that pregnancy is followed by a decrease in PON1 activity and increased risk for development of cardiovascular diseases. We conclude that changes in paraoxonase-1 status during pregnancy are associated with maternal oxidative stress status and smoking habits.Reproductive Toxicology 10/2011; 33(1):20-6. · 3.23 Impact Factor -
Article: Pulmonary function, oxidative stress and inflammatory markers in severe COPD exacerbation.
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ABSTRACT: Oxidative stress and inflammation play an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD). Pulmonary function, oxidative stress parameters and inflammatory markers were measured in 74 patients with severe COPD exacerbation and 41 healthy subjects. In patients all parameters were assessed at two time points: Firstly, one day after admission and secondly, after 7 10 days when they were clinically stable enough to be discharged. Patients were divided in two groups according the presence of ischemic heart disease (IHD): IHD positive (IHD+) patients and IHD negative (IHD-) patients. During hospitalisation O2•-, malondialdehyde (MDA), advanced oxidation protein products (AOPP) and total oxidant status (TOS) increased and were higher at discharge compared with admission and the control group. Superoxide dismutase (SOD) activity was significantly lower in COPD patients at both time points compared with the control group. Total antioxidant status (TAS) was significantly lower and the prooxidant-antioxidant balance (PAB) was higher at both time points in COPD patients compared with the control group. High sensitive C-reactive protein (hsCRP) and also the neutrophil count were significantly higher at admission compared with discharge. Paraoxonase 1 (PON1) enzymatic activities in COPD patients did not differ compared with the control group. IHD+ COPD patients had significantly lower PON1 activity but higher PAB levels and hsCRP concentrations, compared with IHD COPD patients. The oxidant/antioxidant imbalance was significantly pronounced in patients with COPD exacerbation for at least 24 hours following their admission and when they were clinically stable enough to be discharged. Increased oxidative stress, elevated systemic inflammation and decreased antioxidant defence were common in end-stage disease and particularly COPD patients with ischemic heart disease.Respiratory medicine 10/2011; 105 Suppl 1:S31-7. · 2.33 Impact Factor -
Article: Characteristics of low-density and high-density lipoprotein subclasses in pediatric renal transplant recipients.
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ABSTRACT: Renal transplant recipients often suffer from dyslipidemia which is one of the principal risk factors for cardiovascular disease. This study sought to determine characteristics of high-density lipoprotein (HDL) and low-density lipoprotein (LDL) particles and their associations with carotid intima-media thickness (cIMT) in a group of pediatric renal transplant recipients. We also examined the influence of immunosuppressive therapy on measured LDL and HDL particle characteristics. HDL size and subclass distribution were determined using gradient gel electrophoresis, while concentrations of small, dense LDL (sdLDL)-cholesterol (sdLDL-C) and sdLDL-apolipoprotein B (sdLDL-apoB) using heparin-magnesium precipitation method in 21 renal transplant recipients and 32 controls. Renal transplant recipients had less HDL 2b (P < 0.001), but more HDL 3a (P < 0.01) and 3b (P < 0.001) subclasses. They also had increased sdLDL-C (P < 0.01) and sdLDL-apoB (P < 0.05) levels. The proportion of the HDL 3b subclasses was a significant predictor of increased cIMT (P < 0.05). Patients treated with cyclosporine had significantly higher sdLDL-C and sdLDL-apoB concentrations (P < 0.05) when compared with those on tacrolimus therapy. Pediatric renal transplant recipients have impaired distribution of HDL and LDL particles. Changes in the proportion of small-sized HDL particles are significantly associated with cIMT. Advanced lipid testing might be useful in evaluating the effects of immunosuppressive therapy.Transplant International 08/2011; 24(11):1094-102. · 2.92 Impact Factor -
Article: Cox proportional hazard model analysis of survival in end-stage renal disease patients with small-sized high-density lipoprotein particles.
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ABSTRACT: Dyslipidemia is commonly seen in patients with end-stage renal disease (ESRD). This prospective study investigates whether small-sized high-density lipoprotein (HDL) particles alone or in combination with high sensitivity C-reactive protein (hsCRP) are independent determinants of ESRD mortality. We performed 36 months follow-up study in 122 haemodialysis (HD) patients. HDL size and subclass distribution were determined by gradient gel electrophoresis. Baseline characteristics of the patients were evaluated for the prediction of mortality. Cox regressions analysis showed that patients with small-sized HDL particles had 2.8-fold higher risk of lethal outcome (P<0.05). Concomitant presence of small-sized HDL particles and increased hsCRP concentration were significantly associated with reduced survival rate (HR=3.907; P<0.05). Observed relationships persisted after adjustment for serum lipid and lipoprotein concentrations. Our results indicate that small-sized HDL particles alone and combined with elevated hsCRP concentrations are independent predictors of reduced survival in HD patients.Clinical biochemistry 02/2011; 44(8-9):635-41. · 2.02 Impact Factor -
Article: Evaluation of different formulas for LDL-C calculation.
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ABSTRACT: Friedewald's formula for the estimation of LDL-C concentration is the most often used formula in clinical practice. A recent formula by Anandaraja and colleagues for LDL-C estimation still needs to be evaluated before it is extensively applied in diagnosis. In the present study we validated existing formulas and derived a more accurate formula to determine LDL-C in a Serbian population. Our study included 2053 patients with TG < or = 4.52 mmol/L. In an initial group of 1010 patients, Friedewald's and Anandaraja's formulas were compared to a direct homogenous method for LDL-C determination. The obtained results allowed us to modify Friedewald's formula and apply it in a second group of patients. The mean LDL-C concentrations were 3.9 +/- 1.09 mmol/L, 3.63 +/- 1.06 mmol/L and 3.72 +/- 1.04 mmol/L measured by a direct homogenous assay (D-LDL-C), calculated by Friedewald's formula (F-LDL-C) and calculated by Anandaraja's formula (A-LDL-C), respectively in the 1010 patients. The Student's paired t-test showed that D-LDL-C values were significantly higher than F-LDL-C and A-LDL-C values (p < 0.001). The Passing-Bablok regression analysis indicated good correlation between calculated and measured LDL-Cs (r > 0.89). Using lipoprotein values from the initial group we modified Friedewald's formula by replacing the term 2.2 with 3. The new modified formula for LDL-C estimation (S-LDL-C) showed no statistically significant difference compared to D-LDL-C. The absolute bias between these two methods was -0.06 +/- 0.37 mmol/L with a high correlation coefficient (r = 0.96). Our modified formula for LDL-C estimation appears to be more accurate than both Friedewald's and Anandaraja's formulas when applied to a Serbian population.Lipids in Health and Disease 03/2010; 9:27. · 2.17 Impact Factor -
Article: LDL and HDL subclasses in acute ischemic stroke: prediction of risk and short-term mortality.
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ABSTRACT: Small, dense low-density lipoprotein (sdLDL) and small-sized high-density lipoprotein (HDL) particles are established risk factors for ischemic heart disease. However, their clinical significance for acute ischemic stroke (AIS) is uncertain. This study evaluates associations of LDL and HDL particle sizes and subclasses with AIS risk and short-term mortality after AIS. Two hundred AIS patients hospitalised for first-in-a-lifetime stroke and 162 apparently healthy controls were included in the study. LDL and HDL particles were separated by gradient gel electrophoresis and serum lipid parameters were measured by standard laboratory methods. Baseline characteristics of LDL and HDL particles were evaluated for the prediction of AIS and short-term mortality after AIS. AIS patients had significantly more LDL III and IVb, but less LDL I and II particles. They also had significantly smaller HDL size, more HDL 3a, 3b and 3c and less HDL 2b subclasses. The relative content of both sdLDL and small-sized HDL particles was significantly increased in patients (P<0.001 and P<0.001, respectively). In addition, sdLDL was significantly higher in AIS fatalities (n=25) compared with survivors (n=175, P<0.05). Increased sdLDL was a significant predictor of AIS (OR=4.31; P<0.001) and in-hospital mortality after AIS (OR=5.50; P<0.05). The observed relationships persisted after adjustment for conventional risk factors. AIS is associated with adverse distributions of LDL and HDL subclasses. In addition, short-term mortality after AIS is associated with increased sdLDL particles. Our results indicate that sdLDL is an independent predictor of both AIS onset and consecutive short-term mortality.Atherosclerosis 11/2009; 210(2):548-54. · 3.79 Impact Factor -
Article: Excluding deep venous thrombosis in symptomatic outpatients: is fibrin monomer aid to D-dimer analysis?
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ABSTRACT: Many studies have investigated the clinical accuracy of the D-dimer test in combination with pretest probability score for deep venous thrombosis (DVT) exclusion. However, few have evaluated its potential when combined with additional markers such as fibrin monomer. The aim of this study was to test the incremental usefulness of fibrin monomer for DVT screening in a bi-marker approach. This was achieved by adding the fibrin monomer to logistic models that included different D-dimer tests. Plasma concentrations of D-dimer and fibrin monomer were measured in 96 outpatients suspected of having DVT and in 76 patients selected from the total patient group according to pretest probability score (termed the DVT-unlikely group). We constructed receiver operating characteristic curves for three different D-dimer assays. Predictive probabilities from different logistic regression models and pair-wise comparisons of the areas under the receiver operating characteristic curve (AUCs) were calculated without and with fibrin monomer included in the models. For all three D-dimer assays, the AUCs were higher in the DVT-unlikely group compared with AUCs in the total patient group [but the differences were without statistical significance (P > 0.05)]. The calculated fibrin monomer AUCs (0.724 in the total patient group and 0.683 in the DVT-unlikely group) were lower than the D-dimer tests' AUCs. The AUCs obtained from logistic regression models that included the three D-dimer tests in the total patient group and the DVT-unlikely group were significantly increased when fibrin monomer was included in the model to such an extent that the AUCs for one of them indicated outstanding discriminative abilities. Simultaneous D-dimer and fibrin monomer determination provides a more valuable approximation for DVT exclusion compared with just D-dimer analysis. Bearing in mind that the fibrin monomer assay is now both more practical and more suited for routine clinical use, fibrin monomer determination could be a more commonly used parameter together with D-dimer and pretest probability score for DVT diagnosis in the future.Blood coagulation & fibrinolysis: an international journal in haemostasis and thrombosis 09/2009; 20(7):546-51. · 1.25 Impact Factor -
Article: Small, dense LDL cholesterol and apolipoprotein B: relationship with serum lipids and LDL size.
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ABSTRACT: Small, dense low-density lipoprotein-cholesterol (sdLDL-C) is a recently recognised marker of cardiovascular disease risk. On the other hand, the usefulness of sdLDL-apoB concentration determination in clinical practice offers grounds for further exploration. This study investigates the associations of sdLDL-C and sdLDL-apoB with serum lipid parameters and LDL size in healthy men and women. The concentrations of sdLDL-C and sdLDL-apoB were measured after heparin-magnesium precipitation of serum samples from ninety-five asymptomatic subjects (47 men, 30 premenopausal and 18 menopausal women). LDL size was determined by gradient gel electrophoresis and serum lipid and lipoprotein parameters were measured by routine laboratory methods. Compared to premenopausal women, men had higher sdLDL-C (P<0.001) and sdLDL-apoB concentrations (P<0.001). No difference in the sdLDL-C concentration was found between men and menopausal women. Menopause status was associated with higher concentrations of both sdLDL-C (P<0.01) and sdLDL-apoB (P<0.05). Subjects with the LDL B phenotype had elevated sdLDL-C (P<0.01) and sdLDL-apoB concentrations (P<0.001). LDL size and triglycerides were independent determinants of both sdLDL-C and sdLDL-apoB concentrations. Gender and menopausal status have significant impact on sdLDL-C and sdLDL-apoB concentrations. The variability in sdLDL-C and sdLDL-apoB levels is considerably influenced by changes in LDL size and triglyceride concentration. Our results suggest that the characterisation of sdLDL particles by evaluating sdLDL-C could be complemented with sdLDL-apoB determination.Atherosclerosis 07/2009; 207(2):496-501. · 3.79 Impact Factor -
Article: Combined effects of small apolipoprotein (a) isoforms and small, dense LDL on coronary artery disease risk.
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ABSTRACT: Lipoprotein (a) [Lp(a)] consists of low-density lipoprotein (LDL) and apolipoprotein (a) [apo(a)]. Both Lp(a) constituents are well-recognized risk factors for coronary artery disease (CAD). This study investigates the interrelationship of apo(a) and LDL size, as well as their possible synergistic effect on the increase of CAD risk. One hundred nine CAD patients and 102 apparently healthy subjects were included in the study. Lp(a) concentration was measured using immunoturbidimetry. The sizes of apo(a) isoforms were determined by SDS-agarose gel electrophoresis followed by immunoblotting. LDL particle size was determined by gradient gel electrophoresis. We found an inverse correlation between apo(a) size and Lp(a) concentration (r(2) = 31%, p <0.001 in the control group and r(2) = 35%, p <0.001 in the CAD group). Individuals with smaller apo(a) isoforms and small, dense LDL (sdLDL) >50% had the highest risk of CAD development (OR = 4.23, p = 0.017). The synergy index (SIM) for the combination of smaller apo(a) isoforms and sdLDL >50% was 1.2. Adjustment for Lp(a) and triacylglycerol concentrations eliminated smaller apo(a)/sdLDL >50% related risk (p = 0.233 and p = 0.09, respectively). Smaller apo(a) isoforms appear to be superior to sdLDL for the assessment of CAD risk. Their combined effect is synergistic.Archives of medical research 02/2009; 40(1):29-35. · 1.88 Impact Factor -
Article: PON1 status is influenced by oxidative stress and inflammation in coronary heart disease patients.
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ABSTRACT: High-density lipoprotein (HDL) associated paraoxonase 1 (PON1) is an essential component of HDLs' capability to protect low-density lipoproteins (LDL) from oxidative modification and thus to limit the atherosclerotic process. The aim of the current study was to investigate the association between oxidative stress status, indices of inflammation and PON1 status parameters. We determined the relationship between the oxidative stress status, inflammatory markers and PON1 status parameters in 261 middle-aged subjects: 156 coronary heart disease (CHD) patients and 105 CHD-free subjects (as the control group). The PON1 status involved PON1 activity measurements towards two substrates: paraoxon (POase activity) and diazoxon (DZOase activity) and subsequent PON1(Q192R) activity phenotype determination. A statistically significant greater malondialdehyde (MDA) concentration in the RR phenotype subjects compared to QQ subjects within the CHD group was apparent (P<0.05). Multiple linear regression analysis revealed an independent influence of plasmatic SOD activity (P<0.05) on POase values and MDA (P<0.01) and O(2)(-) (P<0.05) on DZOase values. Involvement of inflammatory markers (fibrinogen and hsCRP) in the regression model did not hinder the influence of SOD and MDA on POase and DZOase activities, respectively. Our CHD patients were in a state of oxidative stress, which was most evident in the RR phenotype group. The QQ phenotype group is associated with the lowest oxidative stress status level and also with a better capacity for anti-oxidative protection. Oxidative stress in CHD patients is maintained by systemic low-grade inflammation, which results in PON1 enzymatic activity exhaustion. Therefore, deeper investigation of an effective anti-oxidative and anti-inflammatory therapy should be necessary in order to increase anti-oxidative potency and improve PON1 status of CHD patients.Clinical biochemistry 09/2008; 41(13):1067-73. · 2.02 Impact Factor -
Article: High serum uric acid and low-grade inflammation are associated with smaller LDL and HDL particles.
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ABSTRACT: Elevated serum uric acid (UA) is associated with higher risk for cardiovascular disease (CVD). Smaller, denser low density lipoprotein (LDL) and high-density lipoprotein (HDL) particles are the potential risk factors for CVD, while the role and diagnostic value of inflammatory markers are firmly established. This current cross-sectional study investigates interrelationships between UA, high sensitivity C-reactive protein (hsCRP) and fibrinogen concentrations with LDL and HDL sizes in healthy middle-aged subjects. The outcomes-of-interest were smaller, denser LDL and HDL particles (LDL size <or=25.5nm and HDL size <or=8.8nm). Serum UA, hsCRP and plasma fibrinogen concentrations were measured by standard laboratory methods in a sample of 194 healthy volunteers (112 men and 82 women). LDL and HDL particle sizes were determined by gradient gel electrophoresis. The subjects in the highest UA tertile had significantly smaller LDL and HDL particle sizes (P<0.05 and P<0.01, respectively) and higher concentrations of fibrinogen and hsCRP (P<0.05 and P<0.01, respectively). Elevated UA (>or=318micromol/L) was a significant predictor of smaller, denser LDL and HDL particles (OR=3.09; P<0.01; n=19 and OR=4.40; P<0.001; n=23, respectively). The observed relationship with smaller HDL size persisted after adjustment for conventional cardiovascular risk factors. UA strongly correlated with both markers of inflammation. In addition, the higher hsCRP level correlated with smaller LDL size (P<0.05), while fibrinogen concentration was inversely related to HDL size (P<0.05). Multiple regression analysis revealed that HDL size and inflammatory markers remained independent determinants of UA concentration. In conclusion, higher serum UA and low-grade inflammation are closely linked to alterations in lipoprotein metabolism which may represent an early sign of atherosclerosis in asymptomatic subjects.Atherosclerosis 06/2008; 203(1):236-42. · 3.79 Impact Factor -
Article: Does simultaneous determination of LDL and HDL particle size improve prediction of coronary artery disease risk?
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ABSTRACT: Alterations in plasma lipoprotein subclass distribution affect the risk for coronary artery disease (CAD). However, it is unclear whether the determination of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) phenotypes may or may not improve the ability to predict CAD development. Polyacrylamide gradient (3-31%) gel electrophoresis was used to simultaneously determine size and distribution of lipoprotein subclasses in 181 CAD patients and 178 controls. Mean LDL and HDL subclass sizes were significantly smaller in patients than in controls (p < 0.001). Multivariate logistic regression analysis showed that small dense LDL particles were independent CAD risk predictors (OR = 2.867, p < 0.01), even when adjusted for other traditional risk factors, while small HDL particles lost their significance after adjustment (OR = 2.071, p = 0.054). The area under the ROC curve for LDL (0.671) and HDL (0.643) particle size measurement demonstrated low clinical accuracy when compared to the combination of traditional lipid risk factor measurements. CAD is associated with the predominance of smaller LDL and HDL particles. However, simultaneous determination of these two lipoprotein phenotypes provides no additional power in discriminating CAD and non-CAD subjects, beyond that obtained by the traditional risk factors.Clinical and Experimental Medicine 06/2008; 8(2):109-16. · 1.58 Impact Factor -
Article: Correlation of oxidative stress parameters and inflammatory markers in coronary artery disease patients.
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ABSTRACT: In addition to many traditional risk factors for coronary artery disease (CAD) development, enhanced oxidative stress and inflammation are serious conditions that may also be classified as novel risk factors. In the present study, we assessed the relationship between several parameters of oxidative stress status [malonaldehyde (MDA), superoxide anion (O(2)(-)) and plasma and erythrocyte superoxide dismutase (SOD) activities] with high sensitivity C-reactive protein (hsCRP) and fibrinogen as inflammation markers. Oxidative stress status parameters, inflammation markers and lipid status parameters were measured in 385 subjects [188 coronary heart disease (CHD) patients with angiographically diagnosed coronary artery disease (CAD), 141 patients with occlusion >50% in at least one major coronary artery (CAD+) and 47 patients with occlusion less than 50% (CAD-), and 197 CHD-free middle-aged subjects (the control group)]. The plasma MDA concentration and the level of O(2)(-) in plasma were significantly higher in combination with significantly lower SOD activity in the CAD+ group vs. the control group. By using multiple stepwise regression analysis, fibrinogen and hsCRP showed independent correlation with MDA. Binary logistic regression analysis indicated that both MDA and O(2)(-) were significantly associated with CAD development and adjustment for inflammatory markers weakened this association in the case of MDA. The relationship between oxidative stress parameters and inflammatory species suggest their strong mutual involvement in atherosclerosis development that leads to CAD progression.Clinical Biochemistry 02/2007; 40(3-4):181-7. · 2.08 Impact Factor -
Article: Paraoxonase-1 (PON1) activity, but not PON1(Q192R) phenotype, is a predictor of coronary artery disease in a middle-aged Serbian population.
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ABSTRACT: Paraoxonase-1 (PON1) is a high-density lipoprotein (HDL)-associated serum enzyme that protects lipoproteins from oxidative modifications. Polymorphisms in the gene, including PON1Q192R, have been studied. However, inconsistencies regarding the above-mentioned polymorphism obscure its association with vascular disease. Using a two-substrate (paraoxon/diazoxon) activity method, we investigated the frequencies of PON1Q192R phenotypes in 261 middle-aged subjects: 156 patients with angiographically assessed coronary heart disease (CHD) and 105 CHD-free subjects as the control group. The PON1(192) phenotype was predicted from examination of the two-dimensional plot of hydrolysis rates of diazoxon vs. paraoxon and by using the antimode of the histogram of the ratio of diazoxonase/paraoxonase activity. The PON1Q192R phenotype frequencies in 113 patients with occlusion >50% (coronary artery disease-positive, CAD+ group) vs. control population were as follows: QQ (0.552 vs. 0.510), QR (0.382 vs. 0.408) and RR (0.066 vs. 0.082); chi2=0.414, p=0.813. We found lower paraoxonase (POase) and diazoxonase (DZOase) activities in the CAD+ patients when compared to the control population. According to logistic regression analysis, POase activity was a better predictor of coronary disease onset compared with DZOase activity measurements and PON1Q192R phenotyping. We conclude that enzyme activity (within a particular phenotypic group) is more important than phenotype alone in predicting susceptibility to coronary artery disease.Clinical Chemistry and Laboratory Medicine 02/2006; 44(10):1206-13. · 2.15 Impact Factor
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2009
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University of Belgrade
- Faculty of Pharmacy
Belgrade, SE, Serbia
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