Background:Low levels of antioxidant paraoxonase 1(PON 1)enzyme activity,PON1-Q192R polymorphism(a glutamine(Q)to arginine(R)substitution at position 192),PON1-L55M polymorphism(a leucine(L)to methionine(M)substitutio...Background:Low levels of antioxidant paraoxonase 1(PON 1)enzyme activity,PON1-Q192R polymorphism(a glutamine(Q)to arginine(R)substitution at position 192),PON1-L55M polymorphism(a leucine(L)to methionine(M)substitution at position 55),and oxidized low-density lipoprotein(oxLDL)are risk factors for coronary heart disease.Aerobic exercise improves PON1 activity,but the effects of hypoxic exercise are yet unclear.The aim of this study was to determine the effects of hypoxic underwater rugby training on PON1 activity and oxLDL levels and the role of the mentioned polymorphisms.Methods:Serum PON1 and arylesterase activities(ARE),PON1,PON3,and oxLDL protein levels(by using the enzyme-linked immunosorbent assays)were determined in an athletic group(42 trained male underwater rugby players;age=21.7±4.2 years,mean±SD)and a control group(43 sedentary men;age=23.9±3.2 years).The polymorphisms were determined from genomic DNA samples.Results:PON1 activity(25.1%,p=0.052),PON3(p<0.001),and oxLDL(p<0.001)of the athletic group,including most genotype groups,were higher than those of the control group.In comparison to the controls,PON1 activity levels(p=0.005)of the PON1-Q192R homozygote QQ genotype group and PON1 activity levels(30%,p=0.116)of the PON1-L55M homozygote LL genotype group were higher,whereas ARE activity values of athletic R allele carrier(Rc=QR+RR)(p=0.005)and LL group(p=0.002)were lower than the control genotype groups related to their polymorphisms.Conclusion:Hypoxic training can cause(1)significant oxidative stress,including oxLDL,and an antioxidant response(increase in PON1 activity and PON3),(2)differences in the activity of PON1 and ARE,which are modified by PON1-Q192R and PON1-L55M polymorphisms,respectively,and(3)improvements in PON1 activity of QQ and LL groups.However,hypoxic training can cause a disadvantage of LL and Rc groups for ARE.展开更多
To investigate the malondialdehyde(MDA) levels,paraoxonase1(PON1) activity and 8-hydroxy 2-deoxyguanosine(8-OHd G) levels in the primary open angle glaucoma(POAG) patient.Blood samples from 52 healthy individu...To investigate the malondialdehyde(MDA) levels,paraoxonase1(PON1) activity and 8-hydroxy 2-deoxyguanosine(8-OHd G) levels in the primary open angle glaucoma(POAG) patient.Blood samples from 52 healthy individuals and 53 patients with POAG were analyzed for MDA and 8-OHd G by high-performance liquid chromatography(HPLC) and PON1 by spectrophotometry.The data obtained were analyzed statistically.MDA levels were 10.46±8.4 and 4.70±1.79 μmol; PON1 levels were 121 ±39.55 and 161.62 ±60.22 U/m L; and 8-OHd G values were1.32 ±0.53/10~6 d G and 0.47 ±0.27/10~6 d G in the POAG patients and the control group,respectively.The difference was significant in MDA levels,8-OHd G levels and PON1 activity in POAG patients in comparison with controls(P 〈0.001).We concluded that the observed increase in MDA and 8-OHd G levels may be correlated with decreased PON1 activity.Oxidative stress plays an important role in glaucoma development.展开更多
BACKGROUND: Paraoxonase 1(PON1) is an ester hydro- lase in serum and in the liver. Studies have suggested that PON1 measurement to the current battery of tests may im- prove the evaluation of chronic liver diseases. T...BACKGROUND: Paraoxonase 1(PON1) is an ester hydro- lase in serum and in the liver. Studies have suggested that PON1 measurement to the current battery of tests may im- prove the evaluation of chronic liver diseases. The aim of this study was to investigate the clinical significance of mo- nitoring the level of serum PON1 activity in liver transplan- tation patients. METHODS: A series of biochemical indexes were moni- tored in preoperative, operative and postoperative serum samples of 17 liver-transplanted patients. The change of se- rum PON1 level and its relations with other biochemical in- dexes were analyzed. RESULTS: PON1 was distributed normally in the healthy population and its reference value ranged from 45.5 to 265.8 U/mL. The PON1 level of all patients was lower than that of control group significantly (P<0.001); the level be- gan to elevate continuously 5 minutes after opening of the portal vein and was higher than that 90 minutes after open- ing of the portal vein ( P <0.05). Two days after operation it was still higher than the normal. The levels of serum ALT and AST elevated more significantly after opening of the portal vein than before operation and they were higher than the normal values till 2 days after the operation. CONCLUSIONS: The level of PON1 in serum may be taken as one of the effective indexes to assess whether the implant is alive and to monitor liver function of the patient together with other tests.展开更多
AIMTo investigate the oxidative stress status of the aqueous humor and serum of patients with pseudoexfoliation (PEX) syndrome and pseudoexfoliative glaucoma (PEG) and to measure paraoxonase (PON) and arylesterase (AR...AIMTo investigate the oxidative stress status of the aqueous humor and serum of patients with pseudoexfoliation (PEX) syndrome and pseudoexfoliative glaucoma (PEG) and to measure paraoxonase (PON) and arylesterase (ARE) levels.METHODSA total of 78 patients were enrolled in the study, with 26 patients in each separate group. The patients were divided into three groups: the first group entailed PEX syndrome patients, while the second group consisted of patients with PEG and the third group involved patients with no additional systemic diseases, other than the diagnosis of cataract as control. Total oxidative stress (TOS), total antioxidant capacity (TAC), PON, and ARE levels in aqueous humor and serum were measured.RESULTSTAC, PON and arylesterase levels in aqueous humor and serum of the PEX syndrome and PEG patients were significantly decreased compared with control group (P<0.05). TOS values were higher in patients with PEX syndrome and PEG than controls (P<0.05). TAC, PON and ARE levels of aqueous humor did not differ significantly between the PEX syndrome and PEG groupsCONCLUSIONThese findings are potentially of significance and add to the growing body of evidence for oxidative stress in PEX syndrome and PEG. Decreased antioxidant defense and increased oxidative stress system may play an important role in the pathogenesis of PEX syndrome and PEG.展开更多
Background: Paraoxonase 1 (PON1) is reported to have an antioxidant and cardioprotective properties. Recently, an association of glutamine (Gln) or (type A)/arginine (Arg) or (type B) polymorphism at position 192 of P...Background: Paraoxonase 1 (PON1) is reported to have an antioxidant and cardioprotective properties. Recently, an association of glutamine (Gln) or (type A)/arginine (Arg) or (type B) polymorphism at position 192 of PON1 gene has been suggested with coronary artery disease (CAD) among patients with diabetes mellitus (DM). However, conflicting results have also been reported. Objectives: To investigate the relationship between PON1 gene (Gln192-Arg) poly-morphism and the presence, extent and severity of CAD in type 2 DM. Methods: The study comprised 180 patients recruited from those undergoing coronary angiography for suspected CAD, who were divided according to the presence or absence of CAD and DM into 4 groups;Group I (n = 40 patients) nondiabetic subjects without CAD, Group II (n = 45 patients) diabetic patients without CAD, Group III (n = 47 patients) non diabetic patients with CAD and Group IV (n = 48 patients) diabetic patients with CAD. PON1 (Gln192-Arg) genotype was assessed using polymerase chain reaction (PCR) followed by AlwI digestion. Results: The frequency of Gln allele (Type A) was significantly higher in group I and group II compared to group III and group IV (62.5%, 60% vs 38.3%, 31.25% respectively, p 100 mg/dL [OR 4.31, CI (1.25 - 12.5), P < 0.001], high density lipoprotein (HDL) cholesterol <40 mg/dL [OR 5.11, CI (1.79 - 16.33), P < 0.001] and PON1 192 Arg allele [OR 4.62, CI (1.67 - 13.57), P < 0.001] were significantly independent predictors of CAD. Conclusion: Arg allele of PON1 192 gene polymorphism is an independent risk factor for CAD and it is associated not only with the presence of CAD but also with its extent and severity and its impact is clearly more pronounced in diabetic patients.展开更多
Introduction Single nucleotide polymorphisms (SNPs) are the most abundant DNA markers in the human genome occurring at a frequency of one in every 500--1000 nucleotides. A variety of methods have been used for the ...Introduction Single nucleotide polymorphisms (SNPs) are the most abundant DNA markers in the human genome occurring at a frequency of one in every 500--1000 nucleotides. A variety of methods have been used for the analysis of single nucleotide polymorphisms, including restriction fragment length polymorphism (RFLP), direct sequencing by using laser-induced fluorescence detectionTM, fluorescence energy transfer, MALDI-TOF MS combined with primer extension or invasive cleavage, and fluorescence polarization. During the past two decades, mass spectrometry has become a very popular tool in the analysis of biomolecules and is perfectly suited to the analysis of single nucleotide polymorphisms (SNPs) due to its speed, low cost, and accuracy. In this work, we used MALDI TOF mass spectrometry to detect the fragments of restriction endonuclease hydrolysis of PCR products flanking a SNP located at paraoxonase 1(Q192R). Compared with electrophoresis, this method requires less time of analysis and possess a higher accuracy.展开更多
BACKGROUND: The effect of increased oxidative stress on the development of chronic obstructive pulmonary disease(COPD) is well known. One of the antioxidative systems against oxidative stress in human body is paraoxon...BACKGROUND: The effect of increased oxidative stress on the development of chronic obstructive pulmonary disease(COPD) is well known. One of the antioxidative systems against oxidative stress in human body is paraoxonase(PON) enzyme that protects low density lipoproteins(LDL) against oxidation. This study aimed to explore the polymorphisms on PON1, Q192 R, L55 M genes of patients with COPD.METHODS: DNAs extraction was obtained from blood samples of 50 patients diagnosed with COPD and 50 patients as a control group who were presented to emergency clinic. Genotypes were obtained with polymerase chain reaction(PCR) and AIw I and Hsp92 II restriction enzymes were used for Q192 R and L55 M polymorphisms, respectively. Analysis of data was done with the Chi-square test and Fisher's exact test.RESULTS: A statistically significant difference in Q192 R polymorphism was found between the COPD patients and the control group(P=0.05). There was no statistically significant difference in L55 M polymorphisms between the patient and control groups(P>0.05). Q192 R polymorphism was significantly correlated with the PON1 gene and cigarette smoking; however other risk factors did not show any significant correlation with this polymorphism. Though L55 M polymorphism was significantly correlated with family history and tuberculosis, there was no significant correlation with other risk factors.CONCLUSION: We believe that more studies are needed to study the correlation of L55 M polymorphism with other factors.展开更多
Objective:To observe the effect on the inhibition of coronary atherosclerosis hardening of the paraoxonase gene(PON-1) which transfected to the rabbit epicardial adipose tissue.Methods: Rabbit coronary atherosclerosis...Objective:To observe the effect on the inhibition of coronary atherosclerosis hardening of the paraoxonase gene(PON-1) which transfected to the rabbit epicardial adipose tissue.Methods: Rabbit coronary atherosclerosis model was established by high-fat feeding,liposome-encapsulated recombinant plasmid pEGFP-PON-1 50μL was injected to the rabbit pericardial cavity,and was harvested 4 weeks after transfection.Results:The epicardial fat transfected PON-1 gene had effect on the high lipid level.It significantly increased expression of PON-1 in peripheral arterial vascular tissue(P【0.05);and significantly reduced total cholesterol and low-density lipoprotein cholesterol levels(P【0.05).and the thickness ratio of coronary artery intima/ media(P【0.05).Conclusions:The injection of the PON-1 gene in the pericardial cavity can effectively suppress the formation of coronary atherosclerosis.展开更多
Objective:To investigate the in vitro effects of the antihacterial drugs,mcropenem trihydrate.piperacillin sodium,and cefoperazone sodium,on the activity of human serum paraoxonase mPOND.Methods:hPQN1 was purified fro...Objective:To investigate the in vitro effects of the antihacterial drugs,mcropenem trihydrate.piperacillin sodium,and cefoperazone sodium,on the activity of human serum paraoxonase mPOND.Methods:hPQN1 was purified from human serum using simple chromatographic methods.including DEAE-Sephadex anion exchange and Sephadex G-200 gel filtration chromatography.Results:The three antihacterial drugs decreased in vitro hPON1 activity.Inhibition mechanisms meropcnem trihydrate was noncompetitive while piperacillin sodium and cefoperazone sodium were competitive.Conclusions:Our results showed that antihacterial drugs significantly inhibit hPON1 activity,both in vitro,with rank order meropenem trihydrate piperacillin sodium cefoperazone sodium in vitro.展开更多
Background: Human paraoxonase-2(PON2) which is exclusively intracellular possesses unique properities that distinguish it from PON1 and PON3. Recently, it was demonstrated that PON2 protects against atherosclerosis by...Background: Human paraoxonase-2(PON2) which is exclusively intracellular possesses unique properities that distinguish it from PON1 and PON3. Recently, it was demonstrated that PON2 protects against atherosclerosis by preventing LDL oxidation. Emerging evidences have proposed that genetic variations in the PON2 gene may be associated with coronary artery disease (CAD). Objectives: To investigate the relationship between a common PON2 gene (Cys311-Ser) polymorphism and the presence and extent of CAD. Methods: The study comprised 112 patients recruited from those undergoing coronary angiography for suspected CAD, who were divided according to the presence or absence of CAD into 2 groups Group I including 62 patients with CAD and Group II including 50 patients proved to have normal coronaries. All the subjects included in the study were genotyped for the (Cys311-Ser) polymorphism of PON2 gene using RCR-RFLP. Results: The frequency of Cys allele was significantly higher in group I compared to Group II (77.4% vs. 56% respectively, P < 0.01). Patients with vessel score 3 had significantly higher severity score and higher Cys allele frequency than patients with vessel score 2, the latter group had also significantly higher severity score and Cys allele frequency than patients with vessel score 1. In multivariate logistic regression analysis of different variables for prediction of CAD, age [OR 3.79, CI (1.33 - 12.7), P < 0.01], smoking [OR 0.71, CI (0.23 - 7.81), P 311 Cys allele [OR 5.67, CI (1.99 - 14.77), P < 0.001] were significantly independent predictors of CAD. Conclusion: Cys allele of PON2 311 gene polymorphism is an independent risk factor for CAD and it is associated not only with the presence of CAD but also with its extent and severity.展开更多
Objective:To investigate the effect of paraoxonase 1 gene polymorphism on carotid plaque stability with cerebral infarction in Hainan population.Methods:277 patients of caroticl plaque With cerebral infarction who und...Objective:To investigate the effect of paraoxonase 1 gene polymorphism on carotid plaque stability with cerebral infarction in Hainan population.Methods:277 patients of caroticl plaque With cerebral infarction who underwent physical examination in a hospital in Hainan from 2015 to another awarding 2018 were selected as the experimental group and the 363 people who no cerebral infarction as the Analytical methods:control group.The clinical data analyzed.DNA was collected from peripheral blood of two groups of patients and genotyped by flight mass analytical methods.''AG and GG could be detected by rs3917538.The distribution frequencies of The three genotypes in The control group accorded with Hardy-Weinberg equilibrium.Results:The distribution frequencies of AA,AG and GG in the control group were 97(26.7%),175(48.2%)and 91(25.1%)respectively.In the experimental group,the distribution frequencies were 76(27.4%),136(49.1%)and 65(23.5%).There were no statistical differences among the three detection methods of co-dominant model,Dominant model and recessive model.There was no difference in the frequency of allele A and G between groups.Conclusion:Polymorphism of paraoxonase 1 gene rs3917538 has No significant effect on carotid plaque formation and cerebral infarction in Hainan population.The Supplementary sample size to add more SNP research sites for further study,It is expected to further Revral the relationship between PON1and carotial piaque complicatecl with cerebral infarction in Hainan.展开更多
Objective To ascertain the relationship between paraoxonase gene (PON) and the morbidity of coronary arterial disease (CAD) in Chinese non-insulin-dependent diabetes mellitus (NIDDM) patients. Methods The exons of PON...Objective To ascertain the relationship between paraoxonase gene (PON) and the morbidity of coronary arterial disease (CAD) in Chinese non-insulin-dependent diabetes mellitus (NIDDM) patients. Methods The exons of PON gene were screened by polymerase chain reaction-denaturing gradient gel elec-trophoresis in 49 NIDDM patients complicated with CAD, 49 NIDDM and 101 healthy control cases of Chinese population. Results Gln-Arg191 polymorphism of the PON gene was detected in Chinese with the AIR allele frequency 0.39 and 0. 61 respectively. The genotype distribution (AA, AR and RB) of the PON gene polymor-phism was significantly different between NIDDM patients complicated with CAD and controls (NIDDM and healthy subjects). The former had a significantly higher B allele frequency (0. 79 vs 0. 62 and 0. 61, P < 0. 01). Conclusion Gln-Arg191 polymorphism of the PON gene is associated with CAD morbidity in Chinese NJDDM patients and B allele might be a risk factor.展开更多
Background The oxidative modification of low-density lipoprotein in theartery wall is currently believed to be central to the pathogenesis of atherosclerosis. Paraoxonase(PON1), an enzyme located on high-density lipop...Background The oxidative modification of low-density lipoprotein in theartery wall is currently believed to be central to the pathogenesis of atherosclerosis. Paraoxonase(PON1), an enzyme located on high-density lipoprotein (HDL) , can prevent low-density lipoprotein(LDL) from oxidation at a certain extent. Recent studies show two other members of paraoxonase genefamily, PON2 and PON3, possess antioxidant properties similar to PON1. The aim of the present studywas to explore the role of PON gene cluster on coronary heart disease (CHD) in Chinese Han women.Methods Seven polymorphisms including PON1 -107C > T, -162G > A, -831G > A, R160G, Q192R, PON2S311C, and PON3 -133C > A were genotyped in 184 female patients with CHD and 239 female controls.The plasma PON1 activity toward phenylacetate was determined in 50 cases and 50 controls randomlyselected. Results The plasma PON1 activities were significantly lower in cases than in controls.Individual SNP analysis showed that cases had significantly higher frequencies of PON1 -107T, -831Gand PON2 311S alleles than controls. The genotype distributions of -107C >T were also significantlydifferent between two groups. The odds ratios for the development of CHD were 1. 66 for -107TCcarriers and 2. 0 for -107TT carriers, compared with -107CC carriers. Haplotype analyses showed thatthe distributions of haplotypes comprised of PON1 -107C > T and PON2 S311C were significantlydifferent between cases and controls, with cases having higher frequency of T-S haplotype (44.8% vs.36.3%, P =0.013). The T-S haplotype remained significantly associated with CHD after adjustingenvironmental risk factors (P = 0.0069). Conclusions This association study suggested that lowerplasma PON1 activity increased the risk of CHD in Chinese woman, which may be mediated by the higherfrequency of -107T allele in cases. Haplotype analyses indicated that there might be somesynergistic effects between the PON1 -107C > T and PON2 S311C polymorphisms.展开更多
Background Oxidative stress such as low-density lipoprotein (LDL) oxidation is thought to be an important mechanism in Alzheimer's disease (AD). Paraoxonase 1 (PON1), an enzyme located on high-density lipoprote...Background Oxidative stress such as low-density lipoprotein (LDL) oxidation is thought to be an important mechanism in Alzheimer's disease (AD). Paraoxonase 1 (PON1), an enzyme located on high-density lipoprotein, can prevent LDL from oxidation to some extent. It is also a potent cholinesterase inhibitor and an arylesterase, combating organophosphate poisoning and metabolization of environmental neurotoxins which might be responsible for neurodegeneration with aging.We evaluated the association of Gln192Arg polymorphism in the PON1 gene with AD in a Chinese Han ethnic population. Methods Patients and age-matched controls were recruited from outpatient clinics and a population-based epidemiological survey, respectively. Gln192Arg polymorphism in the PON1 gene was detected by allele-specific PCR technique in 521 patients with AD and 578 healthy controls. Results The presence of at least one of PON1 R alleles (Q/R or R/R) was lower in AD patients than in the controls (82.7% vs 87.4%; χ^2 = 4.68, P = 0.03). PON1 gene R allele frequency was lower in AD patients than in the controls (60.7% vs 64.7%; χ^2=3.85, P = 0.05). One-way ANOVA showed that PON1 genotype had no effect on the age of onset for developing AD. Logistic regression analysis demonstrated the age and sex-adjusted odds ratio (OR) for the risk of AD in PON1 of PON1 R allele carriers was 0.71 (P = 0.044, 95%CI, 0.51 - 0.99).Conclusion Our results indicate that Gln192Arg polymorphism in the PON1 gene is associated with AD, and PON1 R allele might be a protective factor for AD in a Chinese Han ethnic population.展开更多
Cardiac hypertrophy is the strongest predictor of the development of heart failure, and anti-hypertrophic treatment holds the key to improving the clinical syndrome and increasing the survival rates for heart failure....Cardiac hypertrophy is the strongest predictor of the development of heart failure, and anti-hypertrophic treatment holds the key to improving the clinical syndrome and increasing the survival rates for heart failure. The paraoxonase(PON) gene cluster(PC) protects against atherosclerosis and coronary artery diseases. However, the role of PC in the heart is largely unknown. To evaluate the roles of PC in cardiac hypertrophy, transgenic mice carrying the intact human PON1, PON2, and PON3 genes and their flanking sequences were studied. We demonstrated that the PC transgene(PC-Tg) protected mice from cardiac hypertrophy induced by Ang II; these mice had reduced heart weight/body weight ratios, decreased left ventricular wall thicknesses and increased fractional shortening compared with wild-type(WT) control. The same protective tendency was also observed with an Apoe^(-/-)background. Mechanically, PC-Tg normalized the disequilibrium of matrix metalloproteinases(MMPs)/tissue inhibitors of MMPs(TIMPs) in hypertrophic hearts, which might contribute to the protective role of PC-Tg in cardiac fibrosis and, thus, protect against cardiac remodeling. Taken together, our results identify a novel anti-hypertrophic role for the PON gene cluster, suggesting a possible strategy for the treatment of cardiac hypertrophy through elevating the levels of the PON gene family.展开更多
Repeat coronary revascularizations (RCR) are common in patients underwent percutaneous coronary intervention.There is no available prediction model for RCR at present.The association between paraoxonas-1 (PON1) and th...Repeat coronary revascularizations (RCR) are common in patients underwent percutaneous coronary intervention.There is no available prediction model for RCR at present.The association between paraoxonas-1 (PON1) and the development,progression,and prognosis of coronary artery disease is under hot research.The rela-tionship of serum PON1 activity level and RCR has not been reported.This research aimed to detect the difference of serum PON1 activity levels between RCR and single coronary revascularization(SCR) ,hence to illuminate the value of PON1 in predicting RCR.Methods Serum PON1 activity levels of 200 patients who had achieved complete revascu-larizations in first percutaneous coronary intervention (PCI) were determined by colorimetric method.All patients re-ceived one-year follow-up.Coronary angiographies were performed at 6th month.Patients who need more revasculariza-tion procedure during follow-up were enrolled in RCR group; those who did not need more revascularization procedure were enrolled in SCR group.One hundred patients with normal coronary angiography during the same period were setup as non-coronary heart disease control group (NCC) .Results Sixty two patients were enrolled in RCR group (28 with in-stent restenosis,34 with lesion progression in other coronary segments) .Serum PON1 activity levels in RCR group, SCR group and NCC group were 109.2 ± 98.6 μkat/L,132.8 ± 79.4 μkat/L and 156.4 ± 82.8 μkat/L,respective-ly.Statistic differences were found among three groups (P < 0.05) .Conclusions Serum PON1 activity levels are lower in patients who need repeat coronary revascularizations than in patients need single percutaneous coronary inter-vention or without coronary heart disease.A lower serum PON1 activity level is closely associated to repeat coronary re-vascularization.展开更多
Cardiovascular diseases(CVDs)are the leading cause of death globally.CVDs are a group of disorders of the heart and blood vessels and include coronary heart disease,cerebrovascular disease and rheumatic heart disease ...Cardiovascular diseases(CVDs)are the leading cause of death globally.CVDs are a group of disorders of the heart and blood vessels and include coronary heart disease,cerebrovascular disease and rheumatic heart disease among other conditions.There are multiple independent risk factors for CVD,including hypertension,age,smoking,insulin resistance,elevated low-density lipoprotein cholesterol(LDL-C)levels,and triglyceride levels.LDL-C levels have traditionally been the target for therapies aimed at reducing CVD risk.High density lipoprotein(HDL)constitutes the only lipoprotein fraction with atheroprotective functions.Early HDL-targeted therapies have focused on increasing HDL-C levels.However,clinical trials have shown that raising HDL-C with niacin failed to achieve CVD reduction.A possible explanation for these findings is that these drugs could interfere with lipid metabolism and cause alterations in HDL structure and composition,leading to loss of functionality.As a result,targeting HDL-C levels would be insufficient to achieve CVD risk reduction,making HDL functionality a more desirable focus for HDL-directed therapies.There are several drugs which show the potential to improve HDL functionality.These drugs include molecules already approved for human use,such as statins and niacin,and particularly,compounds currently undergoing development such as apolipoprotein A-I mimetics and reconstituted HDL preparations.These therapies show promising potential to improve HDL functionality specifically.Future therapeutic strategies should incorporate HDL functionality as a main target of interest.展开更多
基金Science and Technology Centre unit of Ege University for its financial support(No.33.102.2014.0001)。
文摘Background:Low levels of antioxidant paraoxonase 1(PON 1)enzyme activity,PON1-Q192R polymorphism(a glutamine(Q)to arginine(R)substitution at position 192),PON1-L55M polymorphism(a leucine(L)to methionine(M)substitution at position 55),and oxidized low-density lipoprotein(oxLDL)are risk factors for coronary heart disease.Aerobic exercise improves PON1 activity,but the effects of hypoxic exercise are yet unclear.The aim of this study was to determine the effects of hypoxic underwater rugby training on PON1 activity and oxLDL levels and the role of the mentioned polymorphisms.Methods:Serum PON1 and arylesterase activities(ARE),PON1,PON3,and oxLDL protein levels(by using the enzyme-linked immunosorbent assays)were determined in an athletic group(42 trained male underwater rugby players;age=21.7±4.2 years,mean±SD)and a control group(43 sedentary men;age=23.9±3.2 years).The polymorphisms were determined from genomic DNA samples.Results:PON1 activity(25.1%,p=0.052),PON3(p<0.001),and oxLDL(p<0.001)of the athletic group,including most genotype groups,were higher than those of the control group.In comparison to the controls,PON1 activity levels(p=0.005)of the PON1-Q192R homozygote QQ genotype group and PON1 activity levels(30%,p=0.116)of the PON1-L55M homozygote LL genotype group were higher,whereas ARE activity values of athletic R allele carrier(Rc=QR+RR)(p=0.005)and LL group(p=0.002)were lower than the control genotype groups related to their polymorphisms.Conclusion:Hypoxic training can cause(1)significant oxidative stress,including oxLDL,and an antioxidant response(increase in PON1 activity and PON3),(2)differences in the activity of PON1 and ARE,which are modified by PON1-Q192R and PON1-L55M polymorphisms,respectively,and(3)improvements in PON1 activity of QQ and LL groups.However,hypoxic training can cause a disadvantage of LL and Rc groups for ARE.
文摘To investigate the malondialdehyde(MDA) levels,paraoxonase1(PON1) activity and 8-hydroxy 2-deoxyguanosine(8-OHd G) levels in the primary open angle glaucoma(POAG) patient.Blood samples from 52 healthy individuals and 53 patients with POAG were analyzed for MDA and 8-OHd G by high-performance liquid chromatography(HPLC) and PON1 by spectrophotometry.The data obtained were analyzed statistically.MDA levels were 10.46±8.4 and 4.70±1.79 μmol; PON1 levels were 121 ±39.55 and 161.62 ±60.22 U/m L; and 8-OHd G values were1.32 ±0.53/10~6 d G and 0.47 ±0.27/10~6 d G in the POAG patients and the control group,respectively.The difference was significant in MDA levels,8-OHd G levels and PON1 activity in POAG patients in comparison with controls(P 〈0.001).We concluded that the observed increase in MDA and 8-OHd G levels may be correlated with decreased PON1 activity.Oxidative stress plays an important role in glaucoma development.
文摘BACKGROUND: Paraoxonase 1(PON1) is an ester hydro- lase in serum and in the liver. Studies have suggested that PON1 measurement to the current battery of tests may im- prove the evaluation of chronic liver diseases. The aim of this study was to investigate the clinical significance of mo- nitoring the level of serum PON1 activity in liver transplan- tation patients. METHODS: A series of biochemical indexes were moni- tored in preoperative, operative and postoperative serum samples of 17 liver-transplanted patients. The change of se- rum PON1 level and its relations with other biochemical in- dexes were analyzed. RESULTS: PON1 was distributed normally in the healthy population and its reference value ranged from 45.5 to 265.8 U/mL. The PON1 level of all patients was lower than that of control group significantly (P<0.001); the level be- gan to elevate continuously 5 minutes after opening of the portal vein and was higher than that 90 minutes after open- ing of the portal vein ( P <0.05). Two days after operation it was still higher than the normal. The levels of serum ALT and AST elevated more significantly after opening of the portal vein than before operation and they were higher than the normal values till 2 days after the operation. CONCLUSIONS: The level of PON1 in serum may be taken as one of the effective indexes to assess whether the implant is alive and to monitor liver function of the patient together with other tests.
文摘AIMTo investigate the oxidative stress status of the aqueous humor and serum of patients with pseudoexfoliation (PEX) syndrome and pseudoexfoliative glaucoma (PEG) and to measure paraoxonase (PON) and arylesterase (ARE) levels.METHODSA total of 78 patients were enrolled in the study, with 26 patients in each separate group. The patients were divided into three groups: the first group entailed PEX syndrome patients, while the second group consisted of patients with PEG and the third group involved patients with no additional systemic diseases, other than the diagnosis of cataract as control. Total oxidative stress (TOS), total antioxidant capacity (TAC), PON, and ARE levels in aqueous humor and serum were measured.RESULTSTAC, PON and arylesterase levels in aqueous humor and serum of the PEX syndrome and PEG patients were significantly decreased compared with control group (P<0.05). TOS values were higher in patients with PEX syndrome and PEG than controls (P<0.05). TAC, PON and ARE levels of aqueous humor did not differ significantly between the PEX syndrome and PEG groupsCONCLUSIONThese findings are potentially of significance and add to the growing body of evidence for oxidative stress in PEX syndrome and PEG. Decreased antioxidant defense and increased oxidative stress system may play an important role in the pathogenesis of PEX syndrome and PEG.
文摘Background: Paraoxonase 1 (PON1) is reported to have an antioxidant and cardioprotective properties. Recently, an association of glutamine (Gln) or (type A)/arginine (Arg) or (type B) polymorphism at position 192 of PON1 gene has been suggested with coronary artery disease (CAD) among patients with diabetes mellitus (DM). However, conflicting results have also been reported. Objectives: To investigate the relationship between PON1 gene (Gln192-Arg) poly-morphism and the presence, extent and severity of CAD in type 2 DM. Methods: The study comprised 180 patients recruited from those undergoing coronary angiography for suspected CAD, who were divided according to the presence or absence of CAD and DM into 4 groups;Group I (n = 40 patients) nondiabetic subjects without CAD, Group II (n = 45 patients) diabetic patients without CAD, Group III (n = 47 patients) non diabetic patients with CAD and Group IV (n = 48 patients) diabetic patients with CAD. PON1 (Gln192-Arg) genotype was assessed using polymerase chain reaction (PCR) followed by AlwI digestion. Results: The frequency of Gln allele (Type A) was significantly higher in group I and group II compared to group III and group IV (62.5%, 60% vs 38.3%, 31.25% respectively, p 100 mg/dL [OR 4.31, CI (1.25 - 12.5), P < 0.001], high density lipoprotein (HDL) cholesterol <40 mg/dL [OR 5.11, CI (1.79 - 16.33), P < 0.001] and PON1 192 Arg allele [OR 4.62, CI (1.67 - 13.57), P < 0.001] were significantly independent predictors of CAD. Conclusion: Arg allele of PON1 192 gene polymorphism is an independent risk factor for CAD and it is associated not only with the presence of CAD but also with its extent and severity and its impact is clearly more pronounced in diabetic patients.
文摘Introduction Single nucleotide polymorphisms (SNPs) are the most abundant DNA markers in the human genome occurring at a frequency of one in every 500--1000 nucleotides. A variety of methods have been used for the analysis of single nucleotide polymorphisms, including restriction fragment length polymorphism (RFLP), direct sequencing by using laser-induced fluorescence detectionTM, fluorescence energy transfer, MALDI-TOF MS combined with primer extension or invasive cleavage, and fluorescence polarization. During the past two decades, mass spectrometry has become a very popular tool in the analysis of biomolecules and is perfectly suited to the analysis of single nucleotide polymorphisms (SNPs) due to its speed, low cost, and accuracy. In this work, we used MALDI TOF mass spectrometry to detect the fragments of restriction endonuclease hydrolysis of PCR products flanking a SNP located at paraoxonase 1(Q192R). Compared with electrophoresis, this method requires less time of analysis and possess a higher accuracy.
文摘BACKGROUND: The effect of increased oxidative stress on the development of chronic obstructive pulmonary disease(COPD) is well known. One of the antioxidative systems against oxidative stress in human body is paraoxonase(PON) enzyme that protects low density lipoproteins(LDL) against oxidation. This study aimed to explore the polymorphisms on PON1, Q192 R, L55 M genes of patients with COPD.METHODS: DNAs extraction was obtained from blood samples of 50 patients diagnosed with COPD and 50 patients as a control group who were presented to emergency clinic. Genotypes were obtained with polymerase chain reaction(PCR) and AIw I and Hsp92 II restriction enzymes were used for Q192 R and L55 M polymorphisms, respectively. Analysis of data was done with the Chi-square test and Fisher's exact test.RESULTS: A statistically significant difference in Q192 R polymorphism was found between the COPD patients and the control group(P=0.05). There was no statistically significant difference in L55 M polymorphisms between the patient and control groups(P>0.05). Q192 R polymorphism was significantly correlated with the PON1 gene and cigarette smoking; however other risk factors did not show any significant correlation with this polymorphism. Though L55 M polymorphism was significantly correlated with family history and tuberculosis, there was no significant correlation with other risk factors.CONCLUSION: We believe that more studies are needed to study the correlation of L55 M polymorphism with other factors.
文摘Objective:To observe the effect on the inhibition of coronary atherosclerosis hardening of the paraoxonase gene(PON-1) which transfected to the rabbit epicardial adipose tissue.Methods: Rabbit coronary atherosclerosis model was established by high-fat feeding,liposome-encapsulated recombinant plasmid pEGFP-PON-1 50μL was injected to the rabbit pericardial cavity,and was harvested 4 weeks after transfection.Results:The epicardial fat transfected PON-1 gene had effect on the high lipid level.It significantly increased expression of PON-1 in peripheral arterial vascular tissue(P【0.05);and significantly reduced total cholesterol and low-density lipoprotein cholesterol levels(P【0.05).and the thickness ratio of coronary artery intima/ media(P【0.05).Conclusions:The injection of the PON-1 gene in the pericardial cavity can effectively suppress the formation of coronary atherosclerosis.
基金Supported by Atatrk University Scientific Research Project Fund(BAP-2009/81)
文摘Objective:To investigate the in vitro effects of the antihacterial drugs,mcropenem trihydrate.piperacillin sodium,and cefoperazone sodium,on the activity of human serum paraoxonase mPOND.Methods:hPQN1 was purified from human serum using simple chromatographic methods.including DEAE-Sephadex anion exchange and Sephadex G-200 gel filtration chromatography.Results:The three antihacterial drugs decreased in vitro hPON1 activity.Inhibition mechanisms meropcnem trihydrate was noncompetitive while piperacillin sodium and cefoperazone sodium were competitive.Conclusions:Our results showed that antihacterial drugs significantly inhibit hPON1 activity,both in vitro,with rank order meropenem trihydrate piperacillin sodium cefoperazone sodium in vitro.
文摘Background: Human paraoxonase-2(PON2) which is exclusively intracellular possesses unique properities that distinguish it from PON1 and PON3. Recently, it was demonstrated that PON2 protects against atherosclerosis by preventing LDL oxidation. Emerging evidences have proposed that genetic variations in the PON2 gene may be associated with coronary artery disease (CAD). Objectives: To investigate the relationship between a common PON2 gene (Cys311-Ser) polymorphism and the presence and extent of CAD. Methods: The study comprised 112 patients recruited from those undergoing coronary angiography for suspected CAD, who were divided according to the presence or absence of CAD into 2 groups Group I including 62 patients with CAD and Group II including 50 patients proved to have normal coronaries. All the subjects included in the study were genotyped for the (Cys311-Ser) polymorphism of PON2 gene using RCR-RFLP. Results: The frequency of Cys allele was significantly higher in group I compared to Group II (77.4% vs. 56% respectively, P < 0.01). Patients with vessel score 3 had significantly higher severity score and higher Cys allele frequency than patients with vessel score 2, the latter group had also significantly higher severity score and Cys allele frequency than patients with vessel score 1. In multivariate logistic regression analysis of different variables for prediction of CAD, age [OR 3.79, CI (1.33 - 12.7), P < 0.01], smoking [OR 0.71, CI (0.23 - 7.81), P 311 Cys allele [OR 5.67, CI (1.99 - 14.77), P < 0.001] were significantly independent predictors of CAD. Conclusion: Cys allele of PON2 311 gene polymorphism is an independent risk factor for CAD and it is associated not only with the presence of CAD but also with its extent and severity.
基金Hainan Natural Science Foundation Project(818MS180).
文摘Objective:To investigate the effect of paraoxonase 1 gene polymorphism on carotid plaque stability with cerebral infarction in Hainan population.Methods:277 patients of caroticl plaque With cerebral infarction who underwent physical examination in a hospital in Hainan from 2015 to another awarding 2018 were selected as the experimental group and the 363 people who no cerebral infarction as the Analytical methods:control group.The clinical data analyzed.DNA was collected from peripheral blood of two groups of patients and genotyped by flight mass analytical methods.''AG and GG could be detected by rs3917538.The distribution frequencies of The three genotypes in The control group accorded with Hardy-Weinberg equilibrium.Results:The distribution frequencies of AA,AG and GG in the control group were 97(26.7%),175(48.2%)and 91(25.1%)respectively.In the experimental group,the distribution frequencies were 76(27.4%),136(49.1%)and 65(23.5%).There were no statistical differences among the three detection methods of co-dominant model,Dominant model and recessive model.There was no difference in the frequency of allele A and G between groups.Conclusion:Polymorphism of paraoxonase 1 gene rs3917538 has No significant effect on carotid plaque formation and cerebral infarction in Hainan population.The Supplementary sample size to add more SNP research sites for further study,It is expected to further Revral the relationship between PON1and carotial piaque complicatecl with cerebral infarction in Hainan.
基金grant from Shanghai Science and Technology Com-mission (974119003)
文摘Objective To ascertain the relationship between paraoxonase gene (PON) and the morbidity of coronary arterial disease (CAD) in Chinese non-insulin-dependent diabetes mellitus (NIDDM) patients. Methods The exons of PON gene were screened by polymerase chain reaction-denaturing gradient gel elec-trophoresis in 49 NIDDM patients complicated with CAD, 49 NIDDM and 101 healthy control cases of Chinese population. Results Gln-Arg191 polymorphism of the PON gene was detected in Chinese with the AIR allele frequency 0.39 and 0. 61 respectively. The genotype distribution (AA, AR and RB) of the PON gene polymor-phism was significantly different between NIDDM patients complicated with CAD and controls (NIDDM and healthy subjects). The former had a significantly higher B allele frequency (0. 79 vs 0. 62 and 0. 61, P < 0. 01). Conclusion Gln-Arg191 polymorphism of the PON gene is associated with CAD morbidity in Chinese NJDDM patients and B allele might be a risk factor.
文摘Background The oxidative modification of low-density lipoprotein in theartery wall is currently believed to be central to the pathogenesis of atherosclerosis. Paraoxonase(PON1), an enzyme located on high-density lipoprotein (HDL) , can prevent low-density lipoprotein(LDL) from oxidation at a certain extent. Recent studies show two other members of paraoxonase genefamily, PON2 and PON3, possess antioxidant properties similar to PON1. The aim of the present studywas to explore the role of PON gene cluster on coronary heart disease (CHD) in Chinese Han women.Methods Seven polymorphisms including PON1 -107C > T, -162G > A, -831G > A, R160G, Q192R, PON2S311C, and PON3 -133C > A were genotyped in 184 female patients with CHD and 239 female controls.The plasma PON1 activity toward phenylacetate was determined in 50 cases and 50 controls randomlyselected. Results The plasma PON1 activities were significantly lower in cases than in controls.Individual SNP analysis showed that cases had significantly higher frequencies of PON1 -107T, -831Gand PON2 311S alleles than controls. The genotype distributions of -107C >T were also significantlydifferent between two groups. The odds ratios for the development of CHD were 1. 66 for -107TCcarriers and 2. 0 for -107TT carriers, compared with -107CC carriers. Haplotype analyses showed thatthe distributions of haplotypes comprised of PON1 -107C > T and PON2 S311C were significantlydifferent between cases and controls, with cases having higher frequency of T-S haplotype (44.8% vs.36.3%, P =0.013). The T-S haplotype remained significantly associated with CHD after adjustingenvironmental risk factors (P = 0.0069). Conclusions This association study suggested that lowerplasma PON1 activity increased the risk of CHD in Chinese woman, which may be mediated by the higherfrequency of -107T allele in cases. Haplotype analyses indicated that there might be somesynergistic effects between the PON1 -107C > T and PON2 S311C polymorphisms.
基金This work was supported by grants from the National Committee on Science and Technology, (No. 96-096-05-01) China Medical Board in New York (No. CMB 99-699).
文摘Background Oxidative stress such as low-density lipoprotein (LDL) oxidation is thought to be an important mechanism in Alzheimer's disease (AD). Paraoxonase 1 (PON1), an enzyme located on high-density lipoprotein, can prevent LDL from oxidation to some extent. It is also a potent cholinesterase inhibitor and an arylesterase, combating organophosphate poisoning and metabolization of environmental neurotoxins which might be responsible for neurodegeneration with aging.We evaluated the association of Gln192Arg polymorphism in the PON1 gene with AD in a Chinese Han ethnic population. Methods Patients and age-matched controls were recruited from outpatient clinics and a population-based epidemiological survey, respectively. Gln192Arg polymorphism in the PON1 gene was detected by allele-specific PCR technique in 521 patients with AD and 578 healthy controls. Results The presence of at least one of PON1 R alleles (Q/R or R/R) was lower in AD patients than in the controls (82.7% vs 87.4%; χ^2 = 4.68, P = 0.03). PON1 gene R allele frequency was lower in AD patients than in the controls (60.7% vs 64.7%; χ^2=3.85, P = 0.05). One-way ANOVA showed that PON1 genotype had no effect on the age of onset for developing AD. Logistic regression analysis demonstrated the age and sex-adjusted odds ratio (OR) for the risk of AD in PON1 of PON1 R allele carriers was 0.71 (P = 0.044, 95%CI, 0.51 - 0.99).Conclusion Our results indicate that Gln192Arg polymorphism in the PON1 gene is associated with AD, and PON1 R allele might be a protective factor for AD in a Chinese Han ethnic population.
基金supported by the National Natural Science Foundation of China(81422002,91339201,31271227,31571193)the National Science and Technology Support Project(2013YQ0309230502,2014BAI02B01)the Beijing Nova Program(XX2013064)
文摘Cardiac hypertrophy is the strongest predictor of the development of heart failure, and anti-hypertrophic treatment holds the key to improving the clinical syndrome and increasing the survival rates for heart failure. The paraoxonase(PON) gene cluster(PC) protects against atherosclerosis and coronary artery diseases. However, the role of PC in the heart is largely unknown. To evaluate the roles of PC in cardiac hypertrophy, transgenic mice carrying the intact human PON1, PON2, and PON3 genes and their flanking sequences were studied. We demonstrated that the PC transgene(PC-Tg) protected mice from cardiac hypertrophy induced by Ang II; these mice had reduced heart weight/body weight ratios, decreased left ventricular wall thicknesses and increased fractional shortening compared with wild-type(WT) control. The same protective tendency was also observed with an Apoe^(-/-)background. Mechanically, PC-Tg normalized the disequilibrium of matrix metalloproteinases(MMPs)/tissue inhibitors of MMPs(TIMPs) in hypertrophic hearts, which might contribute to the protective role of PC-Tg in cardiac fibrosis and, thus, protect against cardiac remodeling. Taken together, our results identify a novel anti-hypertrophic role for the PON gene cluster, suggesting a possible strategy for the treatment of cardiac hypertrophy through elevating the levels of the PON gene family.
基金supported by 2009 Shenzhen Health Bureau research project(200903204)
文摘Repeat coronary revascularizations (RCR) are common in patients underwent percutaneous coronary intervention.There is no available prediction model for RCR at present.The association between paraoxonas-1 (PON1) and the development,progression,and prognosis of coronary artery disease is under hot research.The rela-tionship of serum PON1 activity level and RCR has not been reported.This research aimed to detect the difference of serum PON1 activity levels between RCR and single coronary revascularization(SCR) ,hence to illuminate the value of PON1 in predicting RCR.Methods Serum PON1 activity levels of 200 patients who had achieved complete revascu-larizations in first percutaneous coronary intervention (PCI) were determined by colorimetric method.All patients re-ceived one-year follow-up.Coronary angiographies were performed at 6th month.Patients who need more revasculariza-tion procedure during follow-up were enrolled in RCR group; those who did not need more revascularization procedure were enrolled in SCR group.One hundred patients with normal coronary angiography during the same period were setup as non-coronary heart disease control group (NCC) .Results Sixty two patients were enrolled in RCR group (28 with in-stent restenosis,34 with lesion progression in other coronary segments) .Serum PON1 activity levels in RCR group, SCR group and NCC group were 109.2 ± 98.6 μkat/L,132.8 ± 79.4 μkat/L and 156.4 ± 82.8 μkat/L,respective-ly.Statistic differences were found among three groups (P < 0.05) .Conclusions Serum PON1 activity levels are lower in patients who need repeat coronary revascularizations than in patients need single percutaneous coronary inter-vention or without coronary heart disease.A lower serum PON1 activity level is closely associated to repeat coronary re-vascularization.
文摘Cardiovascular diseases(CVDs)are the leading cause of death globally.CVDs are a group of disorders of the heart and blood vessels and include coronary heart disease,cerebrovascular disease and rheumatic heart disease among other conditions.There are multiple independent risk factors for CVD,including hypertension,age,smoking,insulin resistance,elevated low-density lipoprotein cholesterol(LDL-C)levels,and triglyceride levels.LDL-C levels have traditionally been the target for therapies aimed at reducing CVD risk.High density lipoprotein(HDL)constitutes the only lipoprotein fraction with atheroprotective functions.Early HDL-targeted therapies have focused on increasing HDL-C levels.However,clinical trials have shown that raising HDL-C with niacin failed to achieve CVD reduction.A possible explanation for these findings is that these drugs could interfere with lipid metabolism and cause alterations in HDL structure and composition,leading to loss of functionality.As a result,targeting HDL-C levels would be insufficient to achieve CVD risk reduction,making HDL functionality a more desirable focus for HDL-directed therapies.There are several drugs which show the potential to improve HDL functionality.These drugs include molecules already approved for human use,such as statins and niacin,and particularly,compounds currently undergoing development such as apolipoprotein A-I mimetics and reconstituted HDL preparations.These therapies show promising potential to improve HDL functionality specifically.Future therapeutic strategies should incorporate HDL functionality as a main target of interest.