脑梗死患者载脂蛋白E基因多态性与遗传易感性关系

<正>载脂蛋白E(ApoE)是一个含有299个氨基酸并结合有磷脂的糖蛋白,其分子量为34 kD,其结构基因有明显的遗传多态性,可直接参与胆固醇的代谢。研究表明ApoE基因多态性与阿尔茨海默病及血管性痴呆关系密切〔1〕。但ApoE基因多态性与脑梗死的关系,现有的研究结果存在争议。本研究探讨脑梗死患者ApoE基因多态性与遗传易感性的关系。1资料与方法1.1一般资料2010年4月至2011年4月我院健康体检者     

ApoE基因多态性与血脂水平及冠心病的关系

目的 探讨载脂蛋白基因多态性对血脂代谢的影响及冠心病的相关性。方法 对100例冠心病患者和50名正常对照者,采用酶法测定血浆脂质和载脂蛋白（Apo）水平。载脂蛋白E（ApoE）基因型采用聚合酶链反应－限制性片段长度多态性（PCR－RFLP）的方法。结果 冠心病组ApoE4／3基因型高于对照组（P＜0.05）,冠心病患者ApoE4/3基因型携带者总胆固醇和ApoB水平高于其它基因型者（P＜0.05）,其它血脂指标差异无显著性（P＞0.05）。结论 ApoE基因多态性对血脂水平有明显作用,ApoE4基因携带者冠心病的危险性增加。     

温州地区阿尔茨海默病患者精神行为障碍与载脂蛋白E基因多态性的关系

目的 探讨温州地区阿尔茨海默病(AD)患者精神行为障碍与载脂蛋白E(ApoE)基因多态性的关系.方法 收集温州地区AD患者51例,正常对照者54例,采用阿尔茨海默病行为病理评定量表(BEHAVE-AD)进行精神行为测评,采用聚合酶链反应法(PCR)进行ApoE基因分型.结果 AD患者在偏执和妄想、幻觉、行为紊乱和攻击行为方面与正常对照组比较有显著性差异(P<0.05),而ApoE基因检查结果 显示携带ApoEε4基因的AD患者精神行为障碍更为明显.结论 ApoEε4是AD的风险基因,可以作为AD患者早期诊断和治疗的依据.     

ApoE基因多态性的测序检测与阿尔茨海默病的相关性研究

目的探讨载脂蛋白E(ApoE)基因多态性分布及其与阿尔茨海默病(Alzheimer disease,AD)的关系。方法采用基因测序法对212例心脑血管疾病患者和126例健康对照组进行ApoE基因多态性测定,观察其分布情况以及与AD患者的相关性进行分析。结果正常人群ε3/ε3、ε2/ε3、ε4/ε4基因型比例分别为73.0%、12.7%、0.8%,AD组和对照组含ε4等位基因分别为48%、12.7%,差异有统计学意义(P<0.05)。结论ApoEε3/ε3基因型是正常人群的主要形式,ApoEε4等位基因是AD的风险基因之一,与AD的发病呈显著性相关。     

载脂蛋白E基因多态性与老年人群血脂的研究

目的观察载脂蛋白E(ApoE)的遗传多态性与老年人血脂的关系。方法808例受试者,其中脑卒中430例、冠心病167例及对照组211例。采用聚合酶链式反应限制性片段多态性方法检测ApoE基因多态性。结果ApoE4表型携带者的TC、LDLC和ApoB水平显著高于ApoE2表型携带者(P<005),ApoE3/3表型携带者的LDLC水平也高于ApoE2表型携带者(P<005),而ApoE2表型携带者的HDLC水平显著高于ApoE4(P<005),这种作用在男女两性中相似。结论ApoE基因多态性影响老年人群血脂水平,无性别差异。     

载脂蛋白E基因多态性对华法林抗凝疗效的影响

遗传因素是华法林存在个体差异的最重要因素,与药代动力学、药效学及药物转运相关的基因都能够影响华法林的抗凝治疗.近年研究发现,载脂蛋白E(ApoE)基因多态性与华法林个体剂量差异相关.本文就ApoE基因多态性对华法林稳定剂量的影响以及华法林个体化给药方案的研究进展作一综述.     

载脂蛋白E基因多态性与缺血性卒中

载脂蛋白E（apolipoprotein E,ApoE）具有基因多态性（ε2、ε3和ε4）.业已证实,ApoE结构和功能异常与高脂血症和动脉粥样硬化的形成及其严重程度密切相关,而高脂血症和动脉粥样硬化均为缺血性卒中的危险因素.近年来,虽然对ApoE基因多态性与缺血性卒中的关系进行了广泛研究,但结论并不一致.文章就ApoE基因多态性与缺血性卒中相关性的研究进行了综述.     

ApoE基因多态性与心血管疾病的研究进展

载脂蛋白E（ApoE）作为人体内一种广泛存在的调节蛋白，一直是心血管疾病领域的研究热点。目前，已有众多的研究证实ApoE与许多心血管疾病密切相关，并且可能通过脂代谢调节、炎症信号通路激活、抗氧化应激等机制产生作用，尤其是证明了其在冠状动脉粥样硬化性疾病中所发挥的独特作用。但是最近有研究表明，不同的ApoE基因表型在心血管疾病中表现出了不同的作用，甚至是相互矛盾的结果，而且在不同人种、民族、地域和生活习惯的人群中其作用也不尽相同。本文系统阐述了ApoE及其基因表型特征，并着重讨论了ApoE基因多态性在不同心血管疾病中的特殊作用，特别是为探索ApoE基因多态性对国人心血管疾病的影响奠定一定基础。     

载脂蛋白E基因多态性与早发冠心病及血脂含量的关系

目的:研究载脂蛋白E(ApoE)基因多态性与早发冠心病(CHD)的相关关系及其对血脂水平的影响。方法:应用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)基因分析方法,测定92例早发CHD、237例迟发CHD患者和220名对照者的ApoE基因型。血脂水平按常规方法测定。结果:发现的5种ApoE基因型,分别为E3/3、E2/2、E3/2、E4/3及E4/2。早发CHD组和迟发CHD组ApoE4/3基因型和ε4等位基因频率均高于对照组(P<0.05～<0.01);进一步对两组CHD患者的ApoE多态性进行分析,发现早发组ε4等位基因频率较迟发组高(P<0.05)。ApoE各等位基因型的TC和LDL-C水平存在统计学差异(P<0.05)。结论:ApoE基因多态性与早发CHD的发生发展有关,并影响血脂的水平。     

黎族心脑血管疾病患者载脂蛋白E基因多态性与血脂的关系

目的研究海南黎族人群心脑血管疾病载脂蛋白E(ApoE)基因多态性与血脂的关系。方法应用聚合酶链式反应-限制性片段长度多态性(PCR-RFLP)技术检测心脑血管疾病患者150例(高血压50例,脑梗死50例,冠心病50例)ApoE基因多态性分布,同时测定血清总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、载脂蛋白A(ApoA)、载脂蛋白B(ApoB)、脂蛋白a(LPA)成分。结果ε2与ε3基因型比较有LDL-C/HDL-C、ApoB/ApoA、LPA三项有统计学差异、ε3和ε4比较各项指标均无统计学差异。结论降低LPA数值以及ApoB/ApoA和LDL-C/HDL-C比值可能是ε2对心脑血管的保护机制。     

Alzheimer’s disease and type 2 diabetes: the association study of polymorphisms in tumor necrosis factor-alpha and apolipoprotein E genes

Type 2 diabetes (T2D) and Alzheimer??s disease (AD) are two progressive disorders with high prevalence worldwide. Polymorphisms in tumor necrosis factor-alpha (TNF-??) and apolipoprotein E (ApoE) genes might be associated with both T2D and AD, representing possible genetic markers for the development of the AD in subjects with T2D. The aim was to determine ApoE and G-308A TNF-?? gene polymorphisms in unrelated Croatian Caucasians: 207 patients with sporadic AD, 196 T2D patients and 456 healthy controls. Patients with AD had higher frequency of ApoE4 allele compared to T2D patients and controls. The significant association, observed between ApoE2 allele and T2D, disappeared after the data were adjusted for age and sex. The genotype or allele frequencies of G-308A TNF-?? gene polymorphism were similar among the patients with AD, T2D and healthy controls. In conclusion, these results do not support the hypothesis that the A allele of G-308A TNF-?? gene polymorphism is associated either with AD or T2D. Our data confirm the association between the ApoE4 allele and AD, and point out the E2 allele of ApoE gene as the possible risk factor for T2D.     

载脂蛋白E基因多态性与中国人群迟发性阿尔茨海默病相关性的Meta分析

目的系统评价载脂蛋白E(ApoE)基因多态性与中国人群迟发性阿尔茨海默病(LOAD)的相关性。方法计算机检索PubMed、EMbase、CBM、CNKI、WanFang Data和VIP数据库,查找ApoE基因多态性与中国人群LOAD相关性的病例-对照研究,检索时限均为建库至2013年8月12日。由两位研究者进行文献筛选、提取资料,并按照NOS工具进行质量评价后,采用Stata 12.0软件进行Meta分析。结果最终纳入9个病例-对照研究,包括732例LOAD患者,1183例健康对照人群。Meta分析结果显示:基因型ε4/4人群LOAD发病风险是基因型ε3/3人群的16.02倍(OR=16.02,95%CI:7.08~36.27,P0.001);基因型ε3/4人群发病风险是基因型ε3/3人群的3.19倍(OR=3.19,95%CI:2.09~4.87,P0.001);基因型ε2/4人群发病风险是基因型ε3/3人群的3.61倍(OR=3.61,95%CI:1.92~6.79,P0.001);等位基因ε4人群发病风险高于等位基因ε3人群3.71倍(OR=3.71,95%CI:2.49~5.52,P0.001);基因型ε2/3、ε2/2及等位基因ε2人群的发病风险无统计学差异。结论当前证据表明,对于中国人群,ApoE等位基因ε4与LOAD发病有关,且基因型ε4/4是LOAD的高危险因素;等位基因ε2与LOAD发病无相关性。     

阿尔茨海默病的发病机制及营养调节

阿尔茨海默病是一种进行性中枢神经系统退行性疾病,是威胁人类健康的重大疾病之一。目前,阿尔茨海默病的发病机制尚不明确,关于阿尔茨海默病的发病机制有很多学说,对于阿尔茨海默病的治疗效果不理想,但一些营养调节能起到改善的作用,本文即对阿尔茨海默病的发病机制及营养调节研究现状作一综述。     

Isoform-specific interactions of apolipoprotein E with microtubule-associated protein tau: implications for Alzheimer disease.

The apolipoprotein E (apoE) type 4 allele (APOE4) is a susceptibility gene for late-onset familial and sporadic Alzheimer disease. ApoE is found in some neurofibrillary tangle-bearing neurons, one of the major pathologic hallmarks of the disease. Neurofibrillary tangles contain paired helical filaments formed from hyperphosphorylated microtubule-associated protein tau. In vitro, tau binds avidly to apoE3, but not to apoE4, forming a bimolecular complex. Tau phosphorylated with a brain extract does not bind either isoform. ApoE3 binds to the microtubule-binding repeat region of tau, which is also the region that is thought to cause self-assembly into the paired helical filament. Binding studies with fragments of ApoE demonstrate that the tau-binding region of apoE3 corresponds to its receptor-binding domain and is distinct from the region that binds lipoprotein particles or beta/A4 peptide. Isoform-specific interactions of apoE with tau may regulate intraneuronal tau metabolism in Alzheimer disease and alter the rate of formation of paired helical filaments and neurofibrillary tangles.     

Estrogen facilitates neurite extension via apolipoprotein E in cultured adult mouse cortical neurons

Literature review suggests a close relationship between estrogen and apolipoprotein E (ApoE) in the central nervous system. Epidemiology studies show that estrogen replacement therapy (ERT) decreases the morbidity from several chronic neurological diseases. Alleles of ApoE modify the risk for and progression of the same diseases. ApoE levels in the rodent brain vary during the estrous cycle and increase after 17beta-estradiol administration. Both estradiol and ApoE3, the most common isoform of human ApoE, increase the extent of neurite outgrowth in culture. Combined, these observations suggest a common mechanism whereby estrogen may increase ApoE levels to facilitate neurite growth. We tested this hypothesis by characterizing the effects of estradiol and ApoE isoforms on neurite outgrowth in cultured adult mouse cortical neurons. Estradiol increased ApoE levels and neurite outgrowth. ApoE2 increased neurite length more so than ApoE3 in the presence of estradiol. Estradiol had no effect on neurite outgrowth from mice lacking the ApoE gene or when only ApoE4, the isoform of ApoE that is associated with increased risk of neurological disease, was exogenously supplied. Cultures from mice transgenic for human ApoE3 or ApoE4 showed the same isoform-specific effect. Neuronal internalization of recombinant human ApoE3 was greater than ApoE4, and ApoE3 was more effective than ApoE4 in facilitating neuronal uptake of a fatty acid. We conclude that estradiol facilitates neurite growth through an ApoE-dependent mechanism. The effects of ERT on chronic neurological diseases may vary with ApoE genotype. The clinical use of ERT may require ApoE genotyping for optimal efficacy.     

西北地区中老年人群ApoE基因分布特征及血脂水平与认知功能障碍的关系

目的 探讨我国西北地区中老年人群ApoE基因分布特征及其血脂水平与轻度认知障碍（MCI）、阿尔兹海默病（AD）患者发病的关系。方法 以门诊就诊和住院的陕西、甘肃、青海等地区患者为研究对象,根据MCI及AD诊断标准,从中筛查出MCI组120例,AD组64例,正常对照组65例;采用基因芯片法行ApoE基因型测定及血脂检测,并进行统计学分析。结果 本研究中6种基因型均有测出;所选3组人群的ApoE基因型分布符合Hardy-Weinberg遗传平衡定律;3组间的基因型分布E3/E3纯合子频率最高(72.3%),E2/E2型最少（1.5%）,其中,MCI组及AD组E3/E4和E4/E4基因型频率明显高于对照组,而E2/E3型则低于对照组(均P<0.05);MCI组与AD组之间的等位基因分布频率差异无显著性;从血脂水平与基因多态性关系上,AD组患者血清TC、LDL-C水平明显增高,与对照组比较,差异有显著性(P<0.05);MCI及AD组患者中ApoEε4基因型TC、LDL-C 水平明显高于ApoEε2基因型(P<0.05),组间对照显示MCI及AD组ApoEε4基因型TC、LDL-C水平均高于对照组(P<0.05),但MCI与AD组ApoEε4基因型TC、LDL-C水平无明显差异。结论 西北地区中老年人群的ApoE基因分布具有一定的地域特性,其人群MCI及AD的患病与ApoE基因的多态性及血脂水平存在一定的关联。     

老年痴呆患者的危险因子载脂蛋白E 4的研究

目的研究Alzheimer病(AD)与载脂蛋白E(ApoE)基因ε4的相互关系,为AD的实验室诊断提供可能的外周生物学指标.方法我们收集了107例AD患者、68例血管性痴呆(VD)患者及74例年龄、性别相匹配的健康对照组(NDC).均取外周血抗凝,酚、氯仿法提取DNA采用聚合酶链反应(PCR)和限制性片段长度多态性(RFLP)分析技术检测ApoE基因型.结果AD患者中ApoEε4等位基因频率明显高于VD及NDC组(P＜0.01),而VD患者ε4等位基因频率与NDC组间差异无显著性(P＞0.05).在AD患者中,ε4纯合子基因型者的发病年龄较ε4杂合子基因型者明显年轻、ε4杂合子基因型携带者的发病年龄较非ε4基因携带者明显年轻(P值均＜0.05),而VD患者的发病年龄与是否携带ε4等位基因无明显相关性.本研究还发现3例携有ApoEε4/4基因型的家族性痴呆患者.结论ApoEε4与AD密切相关,是AD的危险因子.     

Acute myocardial infarction in young adults: prognostic role of angiotensin-converting enzyme, angiotensin II type I receptor, apolipoprotein E, endothelial constitutive nitric oxide synthase, and glycoprotein IIIa genetic polymorphisms at medium-term follow-up

BACKGROUND: A number of reports have investigated the association between various gene polymorphisms and the phenotypic expression of myocardial infarction. No investigations have evaluated the prognostic role of genetic factors in young people with premature coronary disease. The aim of this study was to investigate the influence of genetic factors compared with that of conventional risk factors on follow-up events in a population of Italian young adults with myocardial infarction. METHODS AND RESULTS: The study population consisted of 106 young patients (mean age 40 +/- 4 years, range 23 to 45 years) with diagnosis of acute myocardial infarction. Clinical and genetic data from the group of patients with events during follow-up were compared with those from patients without events. The following genetic polymorphisms were tested: angiotensin I converting enzyme, angiotensin II type I receptor, apolipoprotein E (ApoE), endothelial constitutive nitric oxide synthase, and platelet glycoprotein IIIa. Coronary angiography was performed in 94 patients. Coronary angiography showed coronary artery disease in 93% of patients. During follow-up (46 +/- 12 months, range 25 to 72) the overall combined end points (cardiac death, myocardial infarction, and revascularization procedures) accounted for 21 events. Family history of coronary artery disease, smoking, stenosis of the left anterior descending artery at coronary angiography, and ApoE polymorphism (presence of epsilon4 allele) were significantly more prevalent (univariate analysis) in the group of patients with events. Logistic multivariate analysis showed that ApoE polymorphism (P =. 004, odds ratio [OR] 6.8, 95% confidence interval [CI] 2 to 22), family history (P =.005, OR 8.3, 95% CI 2 to 35), smoking after acute myocardial infarction (P =.008, OR 10.9, 95% CI 2 to 62), and left anterior descending coronary artery disease (P =.02. OR 6.6, 95% CI 1.3 to 33) were independent predictors of adverse events. CONCLUSIONS: Myocardial infarction at a young age is commonly characterized by evidence of multiple cardiovascular risk factors and by a favorable prognosis in short- and medium-term follow-up. Evidence of significant disease at coronary angiography suggests the presence of a premature atherosclerotic process. ApoE polymorphism (presence of epsilon4 allele) appears to be a strong independent predictor of adverse events, suggesting a remarkable influence in the accelerated coronary disease.     

Aggravated decrease in the activity of nucleus basalis neurons in Alzheimer’s disease is apolipoprotein E-type dependent

As reported before, the metabolic activity of nucleus basalis neurons is reduced significantly in Alzheimer patients. Because the apolipoprotein E (ApoE) 4 genotype is a major risk factor for Alzheimer’s disease (AD), we determined whether the decrease in metabolic activity in nucleus basalis neurons in AD is ApoE-type dependent. The size of the Golgi apparatus (GA) was determined as a measure of neuronal metabolic activity in 30 controls and 41 AD patients with a known ApoE genotype by using an image analysis system in the nucleus basalis of Meynert. A polyclonal antibody directed against MG-160, a sialoglycoprotein of the GA, was used to visualize this organelle. There was a very strong reduction in the size of the GA in the nucleus basalis of AD patients. Furthermore, a strong and significant extra reduction in the size of the GA was found in the nucleus basalis neurons of AD patients with either one or two ApoE 4 alleles compared with Alzheimer patients without ApoE 4 alleles. Our data show that the decreased activity of nucleus basalis neurons in AD is ApoE 4 dependent and suggest that ApoE 4 participates in the pathogenesis of AD by decreasing neuronal metabolism.     

脑梗塞大鼠脑组织水肿与脑脊液ApoE多态性关系

目的：探讨脑梗塞大鼠脑脊液载脂蛋自E（ApoE）基因多态性与周围脑组织水肿的关系。方法：对ApoE基因扩增DNA，进行AfⅠⅢ和HaeⅡ双酶切技术，检测16例脑梗塞大鼠ApoE基因型频率，根据脑梗塞大鼠标本切片计算脑水肿指数，统计学分析它们之间的关系。结果：脑水肿指数与ApoE3呈负相关，而与ApoE4呈正相关，两者都具有统计学意义，脑梗塞大鼠脑脊液ApoE3和ApoE4与周围脑组织水肿具有相关性。结论：脑梗塞大鼠脑脊液ApoE多态性可能是影响周围脑组织水肿的因素之一。