载脂蛋白E与癫痫的关系

载脂蛋白E(apolipoprotein E,ApoE)在中枢神经系统修复受损细胞膜、轴索生长和突触形成的过程中起重要作用.研究证明,在外伤、中毒、免疫应答以及痫性放电引起的脑部损伤的病灶组织中都存在载脂蛋白E表达的上调现象.载脂蛋白E的基因多态性和表达量与难治性癫痫的发生和发展有一定的相关性,提示载脂蛋白E的异常可能是难治性癫痫产生机制中的一个重要环节.     

载脂蛋白E及其等位基因在健康个体和动脉粥样硬化个体中的作用

载脂蛋白E（ApoE）作为LDL、VLDL及其残余受体的配体在脂蛋白代谢中起重要作用．ApoE主要由肝细胞和单核巨噬细胞合成,它有三个共显性的异位体E2、E3、E4,但脂蛋白E2不与LDL和残余受体结合．ApoE的等位基因在个体之间变化频率较大．在欧洲,从南到北,E4等位基因在心血...     

载脂蛋白E对细胞因子表达的免疫调节作用

载脂蛋白E(ApoE)是一种重要的血浆脂蛋白,除调节脂质代谢,在体外能够抑制T淋巴细胞的增殖.近来研究发现ApoE还参与核因子-κB(NF-κB)和促分裂素原活化蛋白激酶(mitogen-activated protein kinases,MAPK)等细胞内多种信号转导,通过对细胞因子表达的调节发挥抗炎和免疫调节作用.本文从ApoE对白细胞介素、干扰素、肿瘤坏死因子、趋化因子等细胞因子的调节作用方面做一概述.     

ApoE4在阿尔茨海默病中的研究进展

载脂蛋白E(apolipoprotein E,ApoE)是一种脂质转运蛋白,在中枢神经系统的神经元中丰富表达,而ApoE4是其中的一种亚型.研究表明ApoE4是阿尔茨海默病(Alzheimer's disease,AD)的危险因素之一,会提高AD的发生率及降低其发病年龄.深入研究ApoE4的结构特性及在AD中的作用机制,有望使其成为诊治AD的靶点.     

ApoE基因多态性与轻度认知障碍的相关性研究

目的 探讨载脂蛋白E(ApoE)基因多态性与轻度认知障碍(mild cognitive impairment,MCI)的关系.方法 应用实时定量荧光PCR方法,检测138例轻度认知障碍患者和134例健康对照者的ApoE基因型,根据ApoE基因型分为基因表现型ApoE2组(ApoE2/E2和ApoE2/E3)、ApoE3...     

ApoE基因多态型与维吾尔族高血压患者的关系

目的：研究载脂蛋白E(ApoE)基因多态型与维吾尔族高血压患者的关系。方法：以载脂蛋白E(ApoE)为候选基因，运用聚合酶链式反应—限制性片段长度多态型(PCR—RFLP)方法检测了70例高血压患者及59例正常对照者的ApoE基因型。结果：载脂蛋白E(ApoE)基因的基因型分布在正常组和高血压患者中有极显著差异(P值与对照比较，P＜O．01)。高血压患者组与正常组比较ApoE基因的等位基因的分布也有极显著差异(两组P＝O．0049，P＜O．01)。维吾尔族高血压患者携带的ε4等位基因的发生率明显较携带其他等位基因患者为高。结论：ε4等位基因可能是维吾尔族高血压患者的一个危险因子。     

载脂蛋白E等位基因频率在日本人和高加索人中的种族差异

载脂蛋白(apo)E等位基因ε_2、ε_3、和ε_4,分别编码三种主要的载脂蛋白E多态蛋白E2、E3和E4,决定着6种载脂蛋白E的表型。载脂蛋白E是极低密度脂蛋白中蛋白质部分的主要成分之一,在脂类代谢中起着重要的作用。     

Apo E对血脂代谢和他汀类调脂药遗传药理学的影响

载脂蛋白E(ApoE)基因多态性决定了各型ApoE结构和功能上的差异 ,其与相应受体的结合能力以及对血脂代谢的影响也存在差异。ApoE基因型与血脂水平和冠心病的发生和发展有一定关系 ;ApoE基因型与他汀类等药物治疗的反应存在交互作用 (遗传药理学 ) ,且可能受到环境因素的影响     

绝经前后妇女载脂蛋白E基因多态性及血脂代谢的分析

为探讨绝经期妇女载脂蛋白E(ApoE)基因多态性的分布情况 ,以及载脂蛋白E基因多态性对绝经期妇女血脂代谢的影响。选取 10 4例绝经后妇女及 92例绝经前妇女 ,采用聚合酶链反应———限制片段长度多态性技术(PCR RFLP)来分析ApoE的基因型 ,并按常规酶法及免疫法测定血脂和载脂蛋白及脂蛋白 (a)。结果显示E3 3基因型及ε3等位基因频率在两组人群中均为最高 ,且在绝经后组中E3 2频率较普通人群明显低 ,在绝经后组中胆固醇(TC)甘油三酯 (TG)、低密度脂蛋白胆固醇 (LDL C)、载脂蛋白B(ApoB)及脂蛋白 (a) (Lp(a) )均显著高于绝经前组 (P<0 0 5 ,P <0 0 1)且在绝经后组中ε4携带者TC ,LDL C ,ApoB明显高于ε3携带者 (P <0 0 5 )。表明载脂蛋白E基因多态性对绝经期妇女血脂的代谢有一定的影响。     

载脂蛋白E基因PCR-RFLP分析方法的建立

目的为研究新疆地区老龄人群载脂蛋白E(ApoE)基因多态性与阿尔茨海默病发病之间的关系而建立一种快速、简便、敏感的对ApoE基因进行多态性分析的方法.方法从抗凝血中提取人全基因组DNA,聚合酶链式反应(PCR)高效扩增ApoE基因,酶切后进行8%非变性聚丙烯酰胺凝胶电泳,凝胶银染色后进行ApoE基因型分析.结果限制性内切酶酶切图谱证实可特异性对ApoE基因进行分型,PCR-RFLP方法在ApoE基因型检测中得到成功建立.     

No relation between apolipoprotein E alleles and obstructive sleep apnea

Apolipoprotein E (ApoE) is a genetic risk factor influencing the development of cardiovascular diseases and Alzheimer's disease. Patients with obstructive sleep apnea (OSA) suffer an excess mortality and morbidity from cardiovascular diseases. The frequencies of ApoE alleles were determined in 291 patients with OSA and 728 controls. The distribution of ApoE alleles and genotypes showed no difference between OSA and controls.     

ApoE ε2/ε3/ε4 polymorphism,ApoC-III/ApoE ratio and metabolic syndrome

Triglyceride-rich lipoproteins contain both apolipoproteins E (ApoE) and C-III (ApoC-III), which show opposite functional properties. The relationships between the ApoE (ε2/ε3/ε4) gene polymorphism and ApoC-III/ApoE ratio has never been investigated. A large population (n=552) of cardiovascular patients, without diabetes and/or lipid-lowering therapy, with or without metabolic syndrome (MetSyn), was genotyped for ε2/ε3/ε4 polymorphism and their ApoCIII/ApoE ratio was evaluated. A second group of patients (n=76) with peripheral artery disease was also genotyped and their ApoC-III/ApoE ratios were measured in HDL and non-HDL fractions. Subjects with E2 had higher and E4 carriers lower TG,ApoE and ApoC-III levels, respectively. The ApoCIII/ ApoE ratio showed an opposite trend, gradually increasing from E2/E2 to E4/E4 subjects. MetSyn patients also had an elevated ApoC-III/ApoE ratio and E4 carriers were more frequent in MetSyn patients (OR 2.08 with a 95%CI 1.22–3.5). The distribution of ApoC-III/ApoE ratio was confirmed also in the second group, with lower values in E2/E3 and higher in E3/E4 subjects. Similar results were obtained for the concentrations measured in non-HDL fractions, but not in the HDL fractions. ApoE ε2/ε/ε4 gene polymorphism is a determinant of the relative proportion of apolipoprotein C-III to E. Carriers of the unfavourable E4 allele present the highest ApoCIII/ApoE ratio and are twofold more frequent among individuals affected by MetSyn. These authors contributed equally to the work     

Apolipoprotein E genotype in Spanish schizophrenic patients

Apolipoprotein E (ApoE) is a lipoprotein that, in the central nervous system, is thought to play a role in neuronal growth and repair. ApoE has three isoforms (ApoE2, ApoE3 and ApoE4) coded by three different alleles (epsilon2, epsilon3 and epsilon4). Evidence from family, twin and adoption studies suggest that there is an important genetic contribution to the etiology of schizophrenia. Schizophrenia is in some cases associated with cognitive impairment similar to that of Alzheimer patients; therefore, one may postulate that the ApoE gene, whose role in the dementia of Alzheimer's type has been clearly demonstrated, may also be involved in schizophrenia. In the present study, we have genotyped 114 schizophrenic Spanish patients and 94 healthy matched controls, and found no association between the ApoE genotype and schizophrenia. Subdivision of patients in clinical subgroups showed a slight increase of ApoE4 in early-age onset of the disease and a slight decrease in positive family history for psychiatric diseases; the group with a poor response to neuroleptic drugs had a lower ApoE2 allele frequency. However, as the differences did not reach statistical significance, we cannot draw evidence of an association. Our negative data do not support an involvement of ApoE in schizophrenia, and suggest that the underlying mechanism for the cognitive impairment found in schizophrenic patients is not related to that of Alzheimer's patients nor to a higher prevalence of the ApoE allele 4.     

Association of apoE gene polymorphisms with lipid metabolism in renal diseases

Background and ObjectivesApolipoprotein E (apoE) plays a central role in the metabolism and homeostasis of lipids. ApoE gene encodes three major isoforms: ε2, ε3 a nd ε4 forming six phenotypes: E2E2, E2E3, E2E4, E3E3, E3E3 and E4E4. Disorders of the lipid metabolism and the homeostasis are frequently coexist in renal diseases. The association between gene polymorphisms of apoE and lipid metabolism were not consistent. This meta-analysis was performed to assess the association between gene polymorphisms of apoE and lipid metabolism in renal diseases.MethodsA pre-defined literatures search and selection of eligible relevant investigations were performed to extract and collect data from electronic databases.ResultsSixteen articles were enrolled for the analysis of association between apoE gene polymorphisms and lipid metabolism. Subjects with E3E4 had a higher total cholesterol (TC) than those with E3E3, and subjects with E2E3 had a lower TC than those with E3E3. Subjects with ε2, had a lower TC than those with ε3 or ε4, and subjects with ε4 had a higher TC than those with, ε3. Subjects with E2E2, E2E3 or E4E4 had a higher triglyceride (TG) than those with E3E3. Subjects with ε4 had a higher TG than those with ε3. Subjects with ε2, had a higher level of TG than those with non-ε2. Subjects with E3E4 had a slightly lower high-density lipoprotein (HDL) than those with E3E3. E3E4 appeared to be associated with lower levels of HDL. Subjects with E2E2, E2E3 had a notably lower low-density lipoprotein (LDL) than those with E3E3. Subjects with ε2, had a lower LDL than those with ε3 or ε4 ApoE gene polymorphisms were not associated with very low-density lipoprotein, and lipoprotein (a) [Lp(a)]. Subjects with E2E3 or E2E4 had higher apoE levels than those with E3E3, and subjects with E4E4 had lower apoE levels than those with E3E3.ConclusionApoE gene polymorphisms are associated with the expression of TC, TG HDL, LDL, Lp(a) or apoE.     

Association between apolipoprotein E genotype,chronic liver disease,and hepatitis B virus

Background/Aims

Apolipoprotein E (ApoE) plays an important role in regulating lipid and lipoprotein metabolism, and ApoE genotypes are known to affect plasma lipoprotein concentrations. We investigated whether ApoE genotype determines the disease outcome in hepatitis B virus (HBV)-infected individuals, and verified the association between ApoE genotype and the occurrence of hepatocellular carcinoma (HCC) in patients with chronic liver diseases of various etiologies.

Methods

This hospital-based, case-controlled study enrolled 156 subjects (47 healthy controls, 50 HBV-related liver cirrhosis patients, and 59 HCC patients). ApoE genotypes were determined using PCR-based ApoE genotyping kits. The biological significance of ApoE genotype was verified by measuring serum ApoE levels using an ELISA kits.

Results

The ε3 allele was the most common allele, with allele frequencies among the entire cohort of 5.8%, 84.3%, and 9.9% for the ε2, ε3, and ε4 alleles, respectively. Significantly more of those patients carrying the ε3/3 genotype had developed liver cirrhosis compared to the control subjects. Being an ApoE4 carrier was associated with a lower probability of developing liver cirrhosis. The allele frequencies and genotype distribution of ApoE did not differ significantly between the liver cirrhosis and HCC patients. The serum level of ApoE was significantly higher in patients with liver cirrhosis than in the healthy controls, but did not differ significantly with the ApoE genotype.

Conclusions

The ApoE ε3/3 genotype frequency was higher in patients with HBV-associated liver cirrhosis than in the controls.     

Apolipoprotein E as vascular risk factor in neurodegenerative dementia

Apolipoprotein E (ApoE) is the major lipid-carrier protein in the brain, and several studies provided evidence that ApoE epsilon4 allele can be considered a genetic risk factor for vascular diseases. Findings indicate that Alzheimer disease (AD) and vascular dementia (VaD) may have common risk factors and/or pathogenesis, but their interrelationships still need to be clearly defined. Since ApoE4 imparts risk for both hyperlipidemia and AD, it seemed worthwhile to investigate the possible role of ApoE in the pathogenesis of AD and VaD. To this task, we examined in healthy volunteers, and AD and VaD patients: i) the frequency of ApoE isoforms; and ii) the influence of ApoE genotype on serum lipid levels. Our findings suggest that epsilon4 allele is an important risk factor for the development not only of the Alzheimer type, but also of the vascular type of dementia. In contrast, epsilon2 allele could have a protective role in AD dementia. These results confirm the hypothesis that serum ApoE concentration is dependent on ApoE genotype, but do not support the view that it has to be considered a relevant biochemical marker for AD and VaD.     

Apolipoprotein E modulates immune activation by acting on the antigen-presenting cell

Apolipoprotein E (ApoE) is synthesized by a variety of cells including macrophages. These cells activate T lymphocytes by antigen presentation, while the T-cell cytokine, interferon-gamma, inhibits macrophage ApoE expression. ApoE inhibits T-cell proliferation in culture but its role in immune responses has been unclear. The ApoE-deficient (E0) mouse permits an evaluation of the immunological role of ApoE. We have analysed T-cell responses to an exogenous antigen (ovalbumin) and polyclonal mitogen (concanavalin A) in E0 and ApoE+/+ mice. Macrophages of E0 mice stimulated T-cell activation more effectively as antigen-presenting cells than macrophages from ApoE+/+ mice. Both proliferation and interferon-gamma secretion were enhanced in T cells activated in the context of antigen-presenting cells from E0 mice. Since the macrophage-T-cell interaction depends on interactions between cell surface molecules, we assessed the expression of such molecules after in vivo stimulation with interferon-gamma. This treatment caused an increased expression of the co-stimulatory surface proteins CD40 and CD80, and also of the major histocompatibility complex class II molecules I-Ab on macrophages of E0 mice compared with ApoE+/+. Our data suggest that ApoE inhibits T-cell activation by reducing the density of immune stimulatory proteins on antigen-presenting cells.     

Dietary restriction reduces atherosclerosis and oxidative stress in the aorta of apolipoprotein E-deficient mice

Dietary restriction (DR) has been shown to inhibit almost all the age-related diseases, e.g. cardiomyopathy and cancers, in rodents. However, there is little information for the effect of DR on atherosclerosis. In the present study, we examined the effect of DR on the development of atherosclerosis in mice homozygous knockout for apolipoprotein E gene (ApoE(-/-)). The ApoE(-/-) mice were fed either ad libitum (AL) or 60% of the diet consumed by the mice fed AL. Atherosclerotic lesions in the proximal aorta of these mice were measured. Our results showed that ApoE(-/-) mice fed the calorie-restricted diet had smaller and relatively early stages of atherosclerotic lesions (e.g. foam cells and free lipids) when compared to ApoE(-/-) mice fed AL, who developed more advanced lesions (e.g. fibrous caps and acellular areas). In addition, ApoE(-/-) mice fed the calorie-restricted diet showed a significant decrease in the level of lipid hydroperoxides and the production of superoxide and hydrogen peroxide in the aorta as compared to ApoE(-/-) mice fed AL. These observations suggest that reduction of oxidative stress in the arterial wall may contribute to the anti-atherogenic effect of DR in ApoE(-/-) mice.     

Therapeutic liver repopulation in a mouse model of hypercholesterolemia

Liver repopulation constitutes an attractive approach for the treatment of liver disorders or of diseases requiring abundant secretion of an active protein. We have described previously a model of selective repopulation of a normal liver by Fas/CD95-resistant hepatocytes, in which we achieved up to 16% hepatocyte repopulation. In the present study, we investigated the therapeutic efficacy of this strategy. With this aim, apolipoprotein E (ApoE) knockout mice were transplanted with Fas/CD95-resistant hepatocytes which constitutively express ApoE. Transplanted mice were submitted to weekly injections of non-lethal doses of the Fas agonist antibody Jo2. After 8 weeks of treatment, we obtained up to 30% of the normal level of plasma ApoE. ApoE secretion was accompanied by a drastic and significant decrease in total plasma cholesterol, which even fell to normal levels. Moreover, this secretion was sufficient to markedly reduce the progression of atherosclerosis. These results demonstrate the efficacy of this repopulation approach for correcting a deficiency in a protein secreted by the liver.