对氧磷酶(Paraoxonase)的测定方法与临床意义

对氧磷酶 (Paraoxonase)是结合在高密度脂蛋白 (HDL)上的一种有机磷三酯化合物水解酶。最近研究表明 ,对氧磷酶可以保护低密度脂蛋白 (LDL)的氧化 ,其活性与基因多态性被认为是动脉粥样硬化、冠心病的独立危险因素。本文综述Paraoxonase的生化特征、基因的多态性。

Serum arylesterase and paraoxonase activity in patients with chronic hepatitis

AIM： To investigate the relationship between serum paraoxonase （PON1）, AST, ALT, GGT, and arylesterase （AE） activity alterations and the degree of liver damage in patients with chronic hepatitis. METHODS： We studied 34 chronic hepatitis patients and 32 control subjects, aged between 35 and 65 years, in the Department of Infection and Clinical Microbiology at the Firat University School of Medicine. Blood samples were collected from subjects between 8：00 and 10：00 a.m. following a 12-h fast. Baseline and salt-stimulated PON1 activities were measured by the hydrolysis of paraoxon. Phenyl acetate was used as the substrate and formed phenol was measured spectrophotometrically at 270 nm after the addition of a 10-fold diluted serum sample in AE activity measurements. RESULTS： The results of this investigation revealed that the levels of AE activity decreased from 132±52 to 94± 36 （29%）, baseline PON1 activity from 452±112 to 164 ±67 （64%）, salt-stimulated PON1 activity from 746± 394 to 294±220 （61%）, HDL from 58.4±5.1 to 47.2±5.6 （200）, triglyceride from 133±51.2 to 86±34.0 （350）, while a slight increase in the level of LDL （from 163± 54.1 to 177.3±56.0; 9%） and significant increases in the levels of AST （from 29±9.3 to 98±44）, ALP （from 57.2±13.1 to 91±38.1）, ALT （from 27.9±3.32 to 89± 19.1）, GGT （from 24.3±2.10 to 94±48.2）, total bilirubin （from 0.74±0.02 to 1.36±0.06; 84%） and direct bilirubin （from 0.18±0.01 to 0.42±0.04; 133%） were detected. However, the levels of albumin, total protein, cholesterol, and uric acid were almost the same in chronic hepatitis and the control subjects.CONCLUSION： Low PON1 and AE activity may contribute to the increased liver dysfunction in chronic hepatitis patients by reducing the ability of HDL to retard LDL oxidation and might be clinically useful for monitoring the disease of chronic hepatitis.

Decreased paraoxonase1 activity and increased malondialdehyde and oxidative DNA damage levels in primary open angle glaucoma

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.

Monitoring the level of serum paraoxonase 1 activity in liver transplantation patients

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.

Total oxidative stress, paraoxonase and arylesterase levels at patients with pseudoexfoliation syndrome and pseudoexfoliative glaucoma

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&#x0003c;0.05). TOS values were higher in patients with PEX syndrome and PEG than controls (P&#x0003c;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.

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

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.

Analysis of Single Nucleotide Polymorphism in Human Paraoxonase 1 Gene(Q192R) with Matrix-assisted Laser Desorption/Ionization Time-of-flight Mass Spectrometry

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.

Paraoxonase-1 gene in patients with chronic obstructive pulmonary disease investigation Q192R and L55M polymorphisms

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.

Inhibitory effect of the paraoxonase gene on the formation of 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.

Impact of antibacterial drugs on human serum paraoxonase-1(hPON1)activity:an in vitro study

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.

Effects of aerobic training on serum paraoxonase activity and its relationship with PON1-192 phenotypes in women

Background：Paraoxonase 1（PON1） is an antioxidant enzyme that protects high-density lipoprotein（HDL） and low-density lipoprotein against oxidation.Limited studies have addressed the influenc of exercise on PON1 activity and its relationship with PON1 phenotypes.We investigated relationships between PON1-192 phenotypes,PON1 activity,aerobic exercise,and blood lipid and lipoprotein concentrations in middle-aged women.Methods：An exercise group（n=50） engaging in regular aerobic exercise and a control group（n=41） were selected from a subset of 300 Caucasian women that met the inclusion criteria.Serum PON1,salt-stimulated PON1（SSPON1）,and arylesterase（ARE） activities;cholesterol levels and ARE activities of total HDL and HDL subgroups（HDLs）（supernatants obtained by polyethylene glycol）;and blood lipid and lipoprotein concentrations were determined by standardized enzymatic methods.PON1-192 QQ（low activity）,QR（moderate activity）,and RR（high activity） phenotype groups were define using serum SSPON1/ARE activity ratios.The R-carries（RC） phenotype group consisted of the QR and RR groups combined.Results：All lipid and lipoprotein concentrations were greater in the exercise group than in the control group.Regardless of phenotype,no significan differences were observed between the exercise and control groups in terms of serum PON1,SSPON1,or ARE activity associated with HDLs（p〉 0.05）,whereas PON1 activities in QQ-phenotyped women in the exercise group were significant y higher than those in the control group（p〈0.01）,but not the RC group.A statistically significan interaction between PON1 phenotypes（QQ and RC groups） and exercise（exercise and control groups） on PON1 activity was found.Conclusion：These results showed that a regular aerobic exercise program can improve PON1 activity depending on PON1-192 phenotype,but not on lipid and lipoprotein levels,in middle-aged Turkish women.

Do PON1-Q192R and PON1-L55M polymorphisms modify the effects of hypoxic training on paraoxonase and arylesterase activity?

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.

Paraoxonase 2 Gene (Cys³¹¹-Ser) Polymorphism and the Risk of Coronary Artery Disease

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.

Pros and Cons in Therapeutic Evaluation of Paraoxonase 1 in Nerve Agent Toxicity

PON 1 （Paraoxonase 1） has been proposed as an efficient catalytic bioscavenger to combat against OP （organophosphate） and CWNA （chemical warfare nerve agent） toxicity. Unlike stoichiometric bioscavengers such as butyrylcholinesterase, catalytic bioscavengers are cost effective with the advantage of eliminating all the OPs/CWNAs at low doses. Analysis of catalytic bioscavenger efficacy of PONI showed promising results by various group of researchers. Still, there are large numbers of grey areas which are not addressed so far. One of the major areas of interest is the pharmacokinetic analysis of infused PON 1 in multiple animal models. It is shown that previous studies in mice significantly increased half-life of PONI, while recent studies in guinea pigs from our group showed reduced half-life of PON1. Similar results were reported by other research groups in guinea pigs and non-human primates. The short half-life of exogenously administered PON1 in multiple animal models may be due to poor association of PON1 with its endogenous carrier, high density lipoprotein or lower doses of PON 1 or a reflection of species difference. These observations warrant the significance of thorough pharmacokinetic analysis of infused PON 1 and the development of alternative approaches for successful utility of PON 1 as an efficient medical countermeasure against OP/CWNA toxicity.

Effect of paraoxonase1 gene polymorphism on carotid plaque and cerebral infarction in Hainan population

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.

Paraoxonase基因簇——1型糖尿病的一种早期微血管并发症遗传标志

Paraoxonase是一糖蛋白,在体内与血清里的高密度脂蛋白(HDL)结合,在体外有防止低密度脂蛋白(LDL)氧化的作用。本文对大样本糖尿病性视网膜病和微蛋白尿病例组,研究PON1和PON2多态性与这两种病的潜在关系。 方法 对拟进行并发症筛选研究的372例1型糖尿病青少年(93％系高加索人)测定其基因型,并作立体眼底照相分级。

STUDY ON THE RELATIONSHIP BETWEEN PARAOXONASE GENE POLYMORPHISM AND CORONARY ARTERIAL DISEASE IN NIDDM

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.

Paraoxonase gene cluster variations associated with coronary heart disease in Chinese Han women

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.

Gln192Arg polymorphism in paraoxonase 1 gene is associated with Alzheimer disease in a Chinese Han ethnic population

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.

Human paraoxonase gene cluster overexpression alleviates angiotensin II-induced cardiac hypertrophy in mice

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.