ABSTRACT
Objective:To preliminarily explore the association between single nucleotide polymorphisms (SNP) of five candidate genes (APH1B, PRNP, HMGCR, SIRT1, ApoE) and Alzheimer′s disease (AD), and to analyze the methylation levels of BAX and ApoE promoters on the pathogenesis of AD.Methods:Seventeen cases who were admitted to the Department of Geriatrics of the First Affiliated Hospital of Xinjiang Medical University from 2014 to 2015 and diagnosed as likely to be AD by geriatrician and neurologists according to the AD diagnostic criteria in 4th Revised Edition of the Diagnostic and Statistical Manual of Mental Disorders of the American Psychiatric Association served AD group, with an age of (75.65±5.86) years, and 34 non-AD patients with matching baseline data such as age, gender, ethnicity, and education status among patients hospitalized during the same period were selected as control group, with an age of (77.59±7.41) years. Sanger sequencing method was used for SNP typing of candidate genes. Methylation-specific polymerase chain reaction was used to determine the DNA methylation level.Results:The distribution of ApoE ε4 allele was statistically different between the AD group and the control group (χ 2=9.718, P=0.002). Candidate genes (SIRT1 rs7895833, APH1B rs1047552, PRNP rs1799990, HMGCR rs3846662) SNP locus genotypes and alleles had no statistically significant differences in the distribution between the AD group and the control group ( P>0.05). After stratification according to whether they carried ApoE ε4, no statistically significant difference was found between the two groups ( P>0.05). The BAX promoter methylation level of the AD group (0.045±0.025) was lower than that of the control group (0.061±0.028) ( t=-2.078, P=0.045). After gender stratification, the BAX methylation level of the female AD group (0.044±0.021) was lower than that of the control group (0.065±0.275) ( t=-2.230, P=0.045). There was no statistically significant difference in the methylation level of ApoE promoter between the AD group and the control group ( P>0.05). After stratification according to whether they carry ApoE ε4 or not, the methylation level of AD patients with ApoE ε4 allele (1.553±0.291) was higher than that of non-carriers (1.221±0.261) ( t=2.480, P=0.025). Conclusions:ApoE ε4 allele may be a risk factor for the onset of AD. BAX promoter hypomethylation contributes to AD in the elderly in Xinjiang, especially in female. ApoE ε4 allele may cause AD through the interaction with ApoE methylation.
ABSTRACT
Objective To investigate the associations of cognitive function with apolipoprotein E (APOE) gene polymorphism and chronic diseases among long-lived people in Zhongxiang City of Hubei Province.Methods A total of 110 long-lived elderly residents aged 90 years and over were collected.Their cognitive function was determined face-to-face using questionnaires by trained interviewers.According to mini-mental state examination(MMSE) scores,subjects were divided into a no dementia risk group and a high dementia risk group.General demographic characteristics,activities of daily living,depression state and nutrition status were compared between the two groups.Correlations of dementia with APOE gene polymorphism and chronic diseases were analyzed.Results The average MMSE score was 22.3±4.8.Among the 110 long-lived people,18 cases had a high risk for dementia,accounting for 16.4％,and 92 cases had no risk of dementia,accounting for 83.6％.The risk of dementia in long-lived elderly people was correlated with activities of daily living,mental state,nutritional status and falls(all P＜0.05).There were 8 cases with the APOE gene ε4/ε3 genotype in the high dementia risk group and 16 cases with the APOE gene ε4/e3 genotype in the no dementia risk group,with the former group showing a higher frequency of the APOE ε4/ε3 genotype (44.4％ vs.17.4％,x2 =6.46,P＜0.05).The former group also seemed to have a higher APOE ε4 frequency,but the difference was not statistically significant(22.2 ％ vs.10.3 ％,x2 =3.96,P =0.055)Chronic diseases prevalent in the long-lived people were hypertension(86 cases,78.2 ％),hearing loss (72 cases,65.5％),hyperlipidemia(56 cases,50.9％),anemia(43 cases,39.1％),impaired vision(39 cases,35.5 ％),chronic kidney diseases(25 cases,22.7 ％),chronic heart diseases (18 cases,16.4 ％) and osteoarthritis(18 cases,16.4％).No correlation was found between the risk of dementia and chronic diseases(P＞0.05).Conclusions Cognitive function is highly correlated with activities of daily living,mental state and nutritional status among long-lived elderly people in Zhongxiang City.The risk of dementia has a correlation with the APOE gene e4/e3 genotype but not with chronic diseases in long-lived people.
ABSTRACT
[Objective]To investigate the effects of different doses of anthocyanins Cy-3-g on serum lipids,platelet-derived chemokines,including MIF and CXCL12 together with their receptors CXCR4 and CXCR7.[Methods]Male ApoE-/-mice were distributed to 5 groups(n=15 per group),and fed with standard diet,high fat diet(HFD),HFD with 200 mg/kg Cy-3-g(low),HFD with 400 mg/kg Cy-3-g(middle),HFD with 800 mg/kg Cy-3-g(high)respectively for 16 weeks. The changes of body weight and food intake were recorded weekly. At the end of the experiment term,the serum lipids(triglyceride,cholesterol,HDL-C,LDL-C)were detected by kits. Arteries were separated to determine plaque histology by Oil-Red-O stain.MIF,CXCL12 and CCL2 in serum were detected by ELISA kits.The expression of CXCR4 and CXCR7 on the surface of leukocytes were tested via flow cytometry. Tail bleeding time was measured mean-while.[Results]Compared with the HFD group,the levels of serum lipids in medium(400 mg/kg)and high(800 mg/kg)Cy-3-g groups were significantly decreased(P<0.05). The plaque area of carotid artery was decreased in high Cy-3-g group(P<0.05).Cy-3-g at all doses significantly reduced the serum concentrations of CXCL12 and CCL2(P<0.002).Cy-3-g of medium(400 mg/kg)and high(800 mg/kg)dose significantly inhibited the expression of CXCR4 and CXCR7 on leukocyte surface(P<0.05). Cy-3-g does not prolong the tail bleeding time.[Conclusions]Anthocyanin Cy-3-g inhibits chemokine CXCL12,CCL2 in serum,and the expression of CXCR4 and CXCR7 on leukocytes without bleeding risk in ApoE-/-mice.
ABSTRACT
Objective To investigate the association between the level of polymorphism of APOE gene and cognitive impairment in patients with CNS demyelinating diseases. Methods 56 patients with central nervous system demyelinating disease were applied APOE genotyping,MoCA and expanded disability status (EDSS) scale score. Patients with MOCA scores <26 were divided into cognitive impairment group, and those with MOCA scores ≥26 were divided into normal cognitive preserved group. Results The probability of cognitive dysfunction in patients with central nervous system demyelinating diseases was 53.57%. There was no significant difference in age, gender, and disease duration between the CI group and the CP group(P>0.05), the difference in age and education among groups is statistically significant (P<0.05). There was no statistical significance in the difference in age, sex, education years and EDSS score between APOEε4 gene positive group and APOEε4 gene negative group (P<0.05). The difference of visual space and attention between different cognitive domains is statistically significant(P<0.05). Years of schooling is a risk factor for cognitive dysfunction in patients with central nervous system demyelinating disease(P<0.01). Conclusion The central nervous system demyelinating disease is impaired cognitive function. Patients with APOEε4 gene positive are more severely impaired in visual space and attention than patients with negative APOEε4 gene.Years of education are the risk factors of cognitive dysfunction in patients with central nervous system demyelinating disease. The course of disease and disabled function may not be significant related to cognitive impairment.
ABSTRACT
Objective To investigate the association between apolipoprotein E(ApoE)gene polymorphism and serum lipoprotein-associated phospholipid(Lp-PLA2)level in patients with AD and sleep disorders. Methods Sixty-two AD patients and 26 healthy controls were enrolled in this study.The polymorphisms of ApoE gene and lev-els of serum Lp-PLA2,IL-6 and other serological indexes were determined,respectively.The mini-mental state ex-amination(MMSE)and Pittsburgh sleep index scale(PSQI)were used to evaluate the cognition and sleep status of AD patients and healthy controls. Results(1)ApoE ε3/4 and ε2/4 genotype were significantly higher in AD patients with sleep disorders(AD-1 group)compared with the healthy controls(P<0 05),and ApoEε3/4 genotype was significantly higher in patients in AD-1 group compared with AD patients without sleep disorder(AD-2 group) (P < 0 05).(2)The ApoEε4 allele frequency in patients in AD-1 group was significantly higher than that in pa-tients in the control group(P<0 05).(3)Levels of serum Lp-PLA2 and IL-6 were significantly higher in AD pa-tients with the ApoEε4 allele compared with AD patients without the ApoEε4 allele(P < 0 05). Conclusion ApoE gene polymorphism has a certain relationship with levels of serum Lp-PLA2 and IL-6 in patients with AD and sleep disturbance,and it′s speculated that the effect of ApoE gene polymorphism on sleep disorder may be associat-ed with inflammatory reaction.
ABSTRACT
Objective To investigate the frequency distribution of ApoE and SLCO1B1 genotypes in abnormal blood lipid lev-els in Xiangya Hospital,explore the correlation of ApoE and SLCO1B1 genotypes with various indicators of dyslipidemia,and provide evidence for prevention and treatment of atherosclerotic diseases.Methods Blood lipid data including TG,TC,LDL-C and HDL-C in 87 cases of dyslipidemia people in Xiangya Hospital from June in 2016 to April in 2017 were collected.The ApoE and SLCO1B1 genotypes were detected by PCR fluoroscopy in 87 cases of dyslipidemia.The distribution of gene fre-quency was analyzed and the differences of blood lipid indexes among the genotypes were compared.Results The frequen-cies of each ApoE genotype in 87 cases of dyslipidemia were E2/E2 1.15%,E2/E3 13.79%,E2/E4 1.15%,E3/E3 56.32%,E3/E4 26.44% and E4/E4 1.15%,respectively.The highest proportion of allele frequency was E3 with the per-cent of 76.44%,E2 and E4 occupied 8.62% and 14.94%,respectively.The concentration of LDL-C in E4 phenotype group was higher than that in E2 group and E3 group,and there was no significant difference in the levels of TG,TC,LDL-C and HDL-C.The frequencies of each SLCO1B1 genotype were *1a/*1a 6.90%,*1a/*1b 36.70%,*1a/*15 13.79%,*1b/*1b 26.44% and *1b/*15 16.09%.The highest frequency of each haplotype was *1b with the percent of 52.87%,*1a and *15 occupied 32.18% and 14.94%,respectively,and no * 5 type was detected.There were no significant differ-ences in TG,TC,LDL-C and HDL-C concentrations between SLCO1B1 groups.Conclusion ApoE gene frequency distribu-tion was uneven.Its polymorphism be related with the lipid levels.The frequency distribution of SLCO1B1 gene had racial differences,and its polymorphism was not related with lipid level.According to the the genotypes of ApoE and SLCO1B1, clinician can choose the right dose of drug to prevent coronary atherosclerotic disease.
ABSTRACT
Objective To discuss the clinical characteristics and prognosis of lipoprotein glomerulopathy (LPG) in chil-dren. Method Clinical data of one pediatric LPG patient were retrospectively analyzed. The clinical features and prognosis of childhood LPG were summarized based on literature review. Results A nine years old girl presented with frequent urination. The ifrst urine test revealed hematuria and proteinuria. After one week anti-infection treatment, the hematuria and proteinuria were continued. The serum albumin was slightly reduced. The hyperlipidemia and mild anemia were emerged. Kidney biopsy showed that enlarged glomeruli, with dilated capillary loops and weak eosinophilic lipoprotein thrombi in the capillary lumina under the light microscope;layered or tuftedemboluscontaining particulated lipid vacuoles under electron microscope. Gene sequencing identified APOE Tokyo (Leu141-Lys143→0). The diagnosis of LPG was confirmed. The lipid-lowering therapy was administrated and the disease was alleviated. Conclusion LPG is a rare disease in children. The level of blood lipid was signiifcantly increased, and the hormone therapy was ineffective. Kidney biopsy is the main basis for diagnosis. The genetic testing can prompt the genetic background. Lipid lowering therapy can relieve the progress of the disease.
ABSTRACT
Aim To observe the effects of the total fla-vonoids of scutellaria barbataon ( TFSB ) on high-fat feeding ApoE gene deficiency mice in early atheroscle-rosis ( AS ) and its underlying mechanisms. Methods 40 ApoE-/ -male mice were divided into five groups:model group, SIM group and L-TFSB, M-TFSB, H-TFSB group, 5 C57BL/6J mice were selected as nor-mal control group. All mice in experimental group were fed with high-lipid diet for 4 weeks and all mice were killed after 8 weeks. H&E staining was used to observe morphology of aorta. Blood rheometer was used to ex-amine plasm viscosity and whole blood viscosity. Fully automatic biochemical analyser was used to detect the serum levels of TG, TC, LDL-C and HDL-C. The ex-pression levels of PLTP and VE in serum were meas-ured by ELISA. The expression levels of PLTP and FXR in liver were examined by Western blot. Results The model was established successfully. TFSB groups could improve the aorta AS morphology of model mice and significantly reduce the serum levels of TG, TC and LDL-C, while increase the level of HDL-C ( P hematocrit value, plasma viscosity and whole blood vis-cosity of AS model mice significantly and had statistical significance when compared with model group ( P <0. 01 ) . The expression levels of PLTP of serum were reduced significantly when compared with model group ( P <0. 01 ) . We also found that the expression of PLTP was in negative correlation with VE ( r = -0. 675,P<0. 01). M-TFSB and H-TFSB group could decrease the expressions of PLTP and FXR of liver when compared with model group ( P <0. 01 ) . Con-clusion TFSB may exert its anti-AS effect partly through inhibiting the levels of FXR and PLTP of ApoE-/ -mice, increasing the level of VE, regulating blood lipids, improving blood rheology and reducing the damage of AS in mice.
ABSTRACT
To investigate the effect on gene expression related cholesterol metabolism in ApoE-/- mice with high-fat-induced insulin resistance(IR). In high-fat fed mice, FBG, FFA, TC, TG, LDL-C, HDL-C, and fasting plasma insulin were significantly higher than those of controls(P＜0.01). The INSIG2 and SCAP mRNA expressions in liver were significantly increased in high-fat fed mice compared with controls(P＜0. 05 or P＜0.01), and INSIG2 protein levels also increased(P＜0. 05). But SREBP1 mRNA expression in liver of high-fat fed mice was significantly reduced(P＜0. 05). These changes might contribute to IR and disorder of cholesterol metabolism in high-fat fed ApoE-/- mice.
ABSTRACT
Antecedentes: La esquizofrenia es una enfermedad mental cuyas causas etiológicas son desconocidas. Los estudios de epidemiología genética, de asociación y de ligamiento, han sugerido la presencia de factores genéticos involucrados en el desarrollo de la esquizofrenia. Existen numerosos estudios dirigidos a comprender la participación del gen de la apolipoproteína E (ApoE) en la esquizofrenia, sin embargo, los resultados son controversiales por la falta de replicación de los hallazgos. Objetivo: Para conocer el efecto del alelo ε4 de ApoE en esquizofrenia, se analizó la frecuencia de genotipos y alelos de ApoE en pacientes de origen mexicano. Resultados y conclusiones: No observamos diferencias estadísticamente significativas en los pacientes con esquizofrenia comparados con el grupo control en las frecuencias por alelos (χ2=0.94, gl=2, p=0.62) ni por genotipos (χ2=1.02, gl=2, p=0.59). Finalmente, el metaanálisis de 19 estudios de asociación, incluyendo el presente estudio, mostró que el alelo de riesgo ε4 de ApoE no está asociado con el desarrollo de la esquizofrenia (OR=1.04, IC 95%=0.90-1.21, p=0.184), sin la presencia de heterogeneidad (χ2=18.8, gl=18, p=0.4).
BACKGROUND: Schizophrenia is a mental disorder of unknown etiology. Epidemiological, association and linkage studies suggest the presence of genetic factors in the development of this disorder. Numerous studies have been undertaken to gain insight on the role of the ApoE gene in schizophrenia. However, findings remain controversial. OBJECTIVE: The current study analyzed the ApoE gene among schizophrenic patients of Mexican origin. RESULTS AND CONCLUSIONS: No significant differences were found in the distribution of alleles (chi2=0.94, df=2, p=0.62), or genotypes (chi2=1.02, df=2, p=0.59). The meta-analysis comprising 19 association studies (including the present one) showed that the risk allele epsilon4 of ApoE is not associated with the development of schizophrenia (OR 1.04, CI 95%=0.90-1.21, p=0.184) in the absence of heterogeneity (chi2=18.8, df=18, p=0.4).
Subject(s)
Humans , Apolipoproteins E/genetics , Schizophrenia/geneticsABSTRACT
Objective To know the apolipoprotein E(APOE)genotypes frequency of Chinese old people in the rural area. Methods 2000 Chinese aged 65 years or older from four sites in China were enrolled in this study in 2004-2008.Two sites were from the Sichuan province in southwestern China,and another two sites were from the Shandong province in eastern China.The finger blood samples on filter paper were collected from all the investigated people in the end of the interview.The genotype for apolipoprotein E(gene symbol,APOE)was determined by eluting DNA from a dried blood spot,followed by HhaI digestion of amplified products.Results Through statistical analysis,APOE genotypes frequency of Chinese people aged 65 years or older in the rural area,as for ?/?2,?2/?3,?2/?4,?3/?3,?3/?4,?4/?4,they were 1.1%,13.55%,2.05%,68.80%,13.35% and 1.15% respectively.4 carriers and no 4 carriers were 16.55% and 83.45%.Conclusion The distribution of APOE 4 genotype is more widely in Chinese people aged 65 years or older in the rural area.
ABSTRACT
The Apolipoprotein E(APOE)gene plays important roles in the pathogenesis of the Alzheimer disease(AD).It is clear that APOE gene is closely related with dementia in the elderly.In recent years,extensive researches regarding the relationship between APOE gene polymorphism and AD has been conducted in both health population and patients with AD using molecular biology technique.This paper reviewed the progress in this field for sharing some fundamental information on the research in AD.
ABSTRACT
Oxidized LDL (ox-LDL) is involved in the initiation and progression of atherosclerosis. Many factors can affect the LDL oxidation such as oxidative stress. The present study tested whether ox-LDL levels would be associated with apolipoprotein E (APOE), manganese superoxide dismutase (MnSOD) Ala16Val polymorphisms, and classic cardiovascular risk factors. ox-LDL levels were measured by thiobarbituric acid-reactive substances and both polymorphisms were determined by polymerase chain reaction/restriction fragment length polymorphism in a sample of 252 subjects (70 men, 182 women, mean age, 54-85 years). Subjects with ox-LDL >or=0.5 nmol/mg apoprotein were considered the high level group (HLG, N = 82) and subjects with ox-LDL <0.5 nmol/mg apoprotein were considered the expected level group (ELG, N = 170). Classic risk factors were also evaluated. The results showed that diabetes mellitus was more prevalent in HLG, whereas other cardiovascular risk factors were similar between groups. The APOE genotype frequencies did not differ between HLG and ELG subjects. However, AA genotype from MnSOD polymorphism was more frequent in ELG (chi(2) = 8.48; P = 0.014). AV and VV subjects from ELG present highest ox-LDL levels (OR = 3.61; CI95% = 1.42-9.17) than AA. Additional analysis did not find gene-gene interactions associated with ox-LDL levels. Multivariate analysis showed that diabetes and the MnSOD polymorphism were independent factors associated with higher ox-LDL levels in HLG. The results suggest that an important framework on modulation of the redox status influenced by genetic polymorphisms could affect the cardiovascular homeostasis.
Subject(s)
Humans , Male , Female , Middle Aged , Aged, 80 and over , Apolipoproteins E/genetics , Cardiovascular Diseases/blood , Lipoproteins, LDL/blood , Polymorphism, Genetic/genetics , Superoxide Dismutase/genetics , Multivariate Analysis , Brazil , Cardiovascular Diseases/genetics , Risk Factors , Genotype , Polymorphism, Restriction Fragment Length , Genetic Predisposition to Disease , Polymerase Chain Reaction , Thiobarbituric Acid Reactive SubstancesABSTRACT
Objective To investigate the effects of liver X receptor agonist on the expressions of C-reactive protein and CD40 ligand and smooth muscle cell ?-actin in the aorta of ApoE gene knockout mice with earlier atherosclerosis. Methods Male ApoE gene knockout mice (8-week old) were divided randomly into control group and T0901317 treatment group (n=6 in each group). The mice in T0901317 group were administered intraperitoneally with T0901317 at the dose of 20 mg?kg-1?d-1 for 4 weeks. Mice in the control group were only given equivalent amount of dimethyl sulfoxide (DMSO). The expressions of C-reactive protein and CD40 ligand and smooth muscle cell ?-actin were detected by immunological histochemical method. Results The expressions of C-reactive protein and CD40 ligand in the atherosclerotic plaque in the aortic wall were significantly lower in T0901317 group as compared with those in the DMSO control group (P0.05). Conclusion Liver X receptor agonist may reduce the formation of atherosclerotic lesions by inhibiting the inflammation and the expressions of C-reactive protein and CD40 ligand in the aorta of ApoE gene knockout mice.
ABSTRACT
Objective To investigate the effects of celastrol on the expressions of macrophage migration inhibitory factor(MIF)and matrix metalloproteinase-9(MMP-9)in the aorta of apoE gene knockout mice with earlier atherosclerosis.Methods Eight-week-old ApoE gene knockout male mice were divided randomly into control group and celastrol treatment group(n=6 in each group).The mice in celastrol group were given.celastrol(2 mg?kg-1?d-1)by intraperitoneal injection for 4 weeks;and the mice in control group were only given equivalent amount of dimethyl sulfoxide(DMSO).HE staining of root aorta were used to observe the histomorphological changes and measure the size of plaque in ApoE-/-mice.The expressions of MIF and MMP-9 were detected by immunological histochemical method.Results The area of lipid plaque in the mice treated with celastrol was significantly smaller than that of the control(P
ABSTRACT
Objective: Studying the relationship between the polymorphism of the apolipoprotein E(ApoE) gene and patients of hypertension. Methods: Using apolipoprotein E (ApoE) gene as a candidate gene, the ApoE gene genotype was determined in 70 patients with hypertension and 59 healthy subjects were studied by the polymerized chain reaction-restriction fragment length polymorphism(PCR-RFLP). Results: The ApoE gene genotype distribution was significantly in healthy subjects and in patients of hypertension(P