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基因多态性与血管性痴呆的关系

人载脂蛋白E（ApoE)具有明显的遗传多态性，3种常见的等位基因（ε2、ε3、ε4）分别编码3种主要异构体（E2、E3、E4）。ApoE作为其受体与低密度脂蛋白（LDL）受体的配基在调节机体脂质水平中起到重要的作用。血管性痴呆是一种多因素，近年来越来越多的学者关注ApoE基因多态性对其发病的作用，并做了大量的研究，但尚未得出一致的结论。     

载脂蛋白E基因多态性与血管性痴呆的关系

人载脂蛋白E(ApoE)具有明显的遗传多态性 ,3种常见的等位基因 (ε2、ε3、ε4 )分别编码 3种主要异构体 (E2、E3、E4 )。ApoE作为其受体与低密度脂蛋白 (LDL)受体的配基在调节机体脂质水平中起到重要的作用。血管性痴呆是一种多因素疾病 ,近年来越来越多的学者关注ApoE基因多态性对其发病的作用 ,并做了大量的研究 ,但尚未得出一致的结论。     

苏中苏南地区高脂血症人群ApoE基因多态性分析研究

目的 为了了解江苏省苏中苏南地区汉族人群高脂血症患者中载脂蛋白E(apolipoprotein E，ApoE)不同基因型的分布差异，从而对他汀类药物在高脂血症患者中的使用提供数据支持，为临床用药提供参考。方法 分别选择2019年8月1日-2022年1月1日在江苏省苏北人民医院和苏州大学第一附属医院诊断为高脂血症患者676例，对患者的ApoE388T＞C（rs429358）、526C＞T（rs7412）相关基因位点的多态性进行了检测，并根据基因分型分为ApoE2、ApoE3和ApoE4三组，搜集纳入各组患者的相关病历数据资料进行回顾性分析，分析总体及不同性别ApoE基因多态性和基因型分布情况，χ2检验分析ApoE基因突变符合 Hardy-weinberg 遗传平衡和进行组间比较，SPSS26.0统计软件分析数据。结果对入选的676例高脂血症病人，三组间患者基本资料中无显著差异（P>0.05），共检出6种ApoE基因表型，由多到少分别为E3/E3 458例(67.75%)，E3/E4 109例（16.12%)，E2/E3 86例（12.72%），E4/E4 11例（1.63%），E2/E4 10例（1.48%），E2/E2 2例（0.30%）。ApoE基因突变符合 Hardy-weinberg 遗传平衡（P>0.05），所有纳入患者来源于同一个孟德尔遗传。ApoE基因型分布在不同性别之间不具有统计学差异(P>0.05)。结论 苏中苏南地区高脂血症人群ApoE的基因多态性分布不均匀，在不同性别中不存在差异，ApoE基因多态性发布特点对临床精准调脂治疗具有一定的参考价值。     

妊娠期高血压疾病患者胎盘组织中ApoE、LPL ser447stop基因多态性检测及意义

目的检测妊娠期高血压疾病(HDP)患者胎盘组织中载脂蛋白E(ApoE)及脂蛋白脂酶(LPL)第9外显子(ser447stop)基因多态性,并探讨其临床意义。方法采用multi-ARMS PCR及PCR-RFLP方法,分别检测36例妊娠期高血压患者(A组)、94例子痫前期患者(B组)及130例正常妊娠妇女(C组)胎盘组织中的ApoE及LPLser447stop基因多态性。结果 A组ApoE2/3、E2/4、E3/3、E3/4及E4/4基因表型频率分别为25.00%、0、50.00%、22.22%、0,B组分别为19.15、0、56.38、24.47%、1.06%,C组分别为14.61%、3.08%、76.92%、5.38%、0.77%。A、B组E3/3、E3/4基因型与C组比较,P均<0.01。A组ApoE等位基因ε2、ε3、ε4频率分别为12.50%、73.61%、11.11%,B组分别为9.57%、78.19%、13.30%,C组分别为8.46%、86.54%、5.00%。A、B组ApoE等位基因ε3、ε4与C组比较,P均<0.05。共检测到3例LPL ser447stop杂合子变异,其中B组2例,C组1例。各组间比较,P均>0.05。结论 HDP患者胎盘组织中ApoE3/4基因表型、ApoEε4等位基因频率增高,ApoEε3等位基因频率降低;ApoE3/4基因表型可能是HDP的危险因素,ApoEε4等位基因可能是HDP的遗传易患因子,而ApoEε3等位基因则具有保护作用。LPL ser447stop基因多态性可能与HDP的发生无关。     

应用生命科学的新成就推动心血管疾病的临床和基础研究

虽然不同的心血管疾病 (如冠心病、心肌梗死、高脂血症等 )的临床表型和发病机制上都是不一样的。但是 ,他们之间包含着许多内在的联系 ,例如 ,脂质紊乱、氧化应激、炎症和血栓形成等。这些疾病的发生、形成包含着大量的基因功能改变、基因与基因的相互作用、基因与环境的相互影响。因此 ,引入生命科学新理念 ,应用其新技术、新方法是推动和提高心血管疾病临床和基础研究水平的关键所在。一、应用单核苷酸多态性和单倍型研究成果开展心血管疾病研究基因多态性或称为单核苷酸多态性 (singlenucleotidepolymorphism ,SNP)是指在基因组水平上…     

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、hs-CRP与冠心病的相关性研究

目的 分析载脂蛋白E(ApoE)的基因多态性、高敏C-反应蛋白(hs-CRP)含量与冠心病的相关性.方法 采用酚氯仿抽提核酸法从凝血块中分离,应用聚合酶链反应(PCR),Hha1内切酶消化法对94例冠心病患者和100例健康对照组进行ApoE基因多态性进行检测;采用生化全自动仪,以乳胶增强免疫透射比浊法检测血清hs-CRP含量.结果 ①ApoE等位基因频率:冠心病组与对照组比较,ε2等位基因频率明显降低(P＜0.01),ε4等位基因频率升高(P＜0.005);②血清hs-CRP浓度,冠心病组显著升高(P＜0.05),但不同等位基因之间,hs-CRP无显著性差别(P＞0.05).结论 联合监测ApoE基因多态性及血清hs-CRP含量,对心血管疾病危险性的预测是敏感及有价值的指标.     

载脂蛋白E基因多态性与不同年龄段腔隙性梗死关系的研究

目的:探讨载脂蛋白E(ApoE)基因多态性与不同年龄段腔隙性梗死(lacunar infarction)的相关性。方法:采用病例对照研究,对105例中老年腔隙性梗死患者和322例健康对照者进行研究。用多聚合酶链式反应(PCR)和限制性片段长度多态性测定ApoE基因多态性。结果:ApoE各基因型和等位基因频率在同年龄组的腔隙性梗死和对照组之间差异无显著性(P>0.05)。结论:未发现ApoE基因多态性与不同年龄群的腔隙性梗死存在相关关系。对于不同年龄段应采取不同的一级预防措施。     

载脂蛋白E基因多态性与颈动脉粥样硬化性狭窄的相关性研究

目的研究载脂蛋白E（ApoE）多态性在颈动脉粥样硬化性狭窄发病中的作用。方法应用聚合酶链反应一限制性片段长度多态性（PCR．RELP）技术，对25例颈动脉粥样硬化性狭窄患者（狭窄组）和25例同期健康体检者（对照组）的ApoE基因多态性进行分析。结果与对照组比较，狭窄组ε3频率降低（P〈0．05），ε4频率升高（P〈0．01），ε3／ε4和ε4／ε4基因型频率增高（P〈0．05、0．01）；对以上两组再按ApoE基因型分别分为ApoE2（ε2／2＋ε2／3）、ApoE3（ε3／3）、ApoFA（ε3／4＋ε4／4）；其中ApoE4狭窄程度增加。结论ApoE基因多态性与颈动脉粥样硬化性狭窄形成有相关性，ε4基因是颈动脉粥样硬化性狭窄形成的危险因子。     

Apolipoprotein E-related all-cause mortality in hospitalized elderly patients

The most common apolipoprotein E (APOE) allelic variation is implicated in many age-related diseases and human longevity with controversial findings. We investigated the effect of APOE gene polymorphism on all-cause mortality in elderly patients taking into consideration the functional disability, cognitive impairment, malnutrition, and the occurrence of common age-related diseases. APOE genotypes were determined in 2,124 geriatric hospitalized patients (46.5% men and 53.5% women; mean age, 78.2 ± 7.1 years; range, 65–100 years). At hospital admission, all patients underwent a comprehensive geriatric assessment to evaluate functional disability, cognitive status, nutritional status, and comorbidity. The main and secondary diagnoses at hospital discharge were also recorded. Mortality status was evaluated in all patients after a maximum follow-up of 5 years (range, from 1.26 to 5.23 years; median, 2.86 years). During the study period, 671 patients died (32.0%). At hospital admission, these patients showed a significant higher prevalence of cardiovascular diseases (56.3% vs 53.4%; p = 0.007), neoplasias (32.3% vs 13.7%; p < 0.001), and lower prevalence of neurodegenerative diseases (17.7% vs 20.7%; p < 0.001) than survived patients. Moreover, they also showed an higher prevalence of disability (52.0% vs 25.6%; p < 0.001), cognitive impairment (31.0% vs 18.8%; p < 0.001), and malnutrition (74.0% vs 46.1%; p < 0.001) than survived patients. In the overall study population, the APOE ε2 allele was significantly associated to neurodegenerative diseases (odds ratio = 0.59; 95% confidence interval (CI), 0.37–0.94). No significant association between the APOE polymorphism and disability, malnutrition, co-morbidity status, and with all-cause mortality was observed. In patients with cardiovascular diseases, however, a decreased risk of all-cause mortality was found in the ε2 allele carriers (hazard ratio = 0.56; 95% CI, 0.36–0.88). In this population, APOE allele variants might play a role on cardiovascular disease-related mortality.     

Large-scale evidence that the cardiotoxicity of smoking is not significantly modified by the apolipoprotein E epsilon2/epsilon3/epsilon4 genotype

Results from two small studies, involving a total of only 174 cases, have suggested that the increased risk of coronary heart disease conferred by cigarette smoking is substantially affected by genotype at the apolipoprotein E (APOE) epsilon2/epsilon3/epsilon4 polymorphism. We have established APOE genotypes in 4484 patients with acute myocardial infarction diagnosed before the age of 55 years for male and 65 years for female patients, and in 5757 controls with no history of cardiovascular disease. On average, the hazard ratio for myocardial infarction was 1.17 (95% CI 1.09-1.25; p<0.00001) per stepwise change from epsilon3/2 to epsilon3/3 to epsilon3/4 genotype. Among individuals in this study with known cigarette smoking status, the hazard ratio for myocardial infarction in smokers versus non-smokers was 4.6 (4.2-5.1). There was, however, no significant difference between the smoker/non-smoker hazard ratios for those with different APOE genotypes (chi2(2)=0.69; p=0.7). When differences in risk between different genotypes are not extreme (as with this APOE polymorphism), reliable assessment of hypothesised gene-environment interactions will often require the study of many thousands of disease cases.     

Polymorphism of the renin-angiotensin system and renal failure

The renin-angiotenin-aldosterone system (RAAS) is not only involved in cardiovascular disease but also in renal pathophysiology and progression of renal disease. Several polymorphisms of genes coding for components of the RAAS have been identified. The I/D polymorphism of the ACE gene, a variant of the angiotensiogen gen, the M235T polymorphism, and the variant A1166 C polymorphism of the angiotensin II type 1 receptor gene are the most important. Several studies have suggested a potential role for I/D polymorphism of the ACE gen in the progression of renal diseases and in the cardiovascular death rate of patients with renal failure. Data on RAAS polymorphisms as determinants of the prevalence of renal diseases and the response to renoprotective therapies are conflicting. Given the polygenic nature of renal and cardiovascular disease and the growing number of candidate genes, large prospective and collaborative studies are required to assess the effect of RAAS polymorphisms on the progression of renal disease and on the response to renoprotective therapies.     

The genetics of the human APOE polymorphism

Abstract The genetic origin of the three common variants of the human apolipoprotein E (apoE) protein, known as E2, E3 and E4, was understood in 1981, and since the mid 1980s these are probably the most-studied protein variants in human races. They have been related to a number of age-related diseases, including Alzheimer disease, as well as to healthy aging and longevity. The gene variants underlying these protein isoforms, known as ε2, ε3, and ε4, are allelic forms of the APOE gene, resulting from different haplotypes at the APOE locus (19q13.31). In particular, they result from three of the four haplotypes expected by the combinations of the alleles of the two single-nucleotide polymorphisms rs429358 and rs7412. The fourth missing haplotype, known as ε3r, has been identified in only two Caucasian families from Italy and in one Yoruba family from Nigeria worldwide. Thus, this fourth APOE gene variant is rare, and it encodes a protein isoform, identified as E3r, showing identical physical characteristics to E3, that conversely, is the most common form of apoE in humans. In this review article, we report the identification of the haplotype ε3r in a third Caucasian family from Italy, and then attempt to re-examine the current knowledge regarding the APOE polymorphism, taking into account this fourth haplotype. We also focus on the commonly accepted hypothesis for the evolution of the common APOE gene variants, in which we include the ε3r haplotype, previously not considered.     

细胞色素氧化酶CYP2C9基因多态性及其与心血管药物代谢及疾病关系研究进展

细胞色素氧化酶P4502C9是人类肝脏中一种重要药物代谢酶,代谢约10%临床上常用药物,包括一些心血管系统疾病的用药。细胞色素氧化酶P4502C9基因具有高度多态性,在基因编码区和非编码区存在许多单碱基突变,这种基因多态性对心血管系统疾病的一些重要用药的代谢差异产生重要的影响,并可能和某些疾病的发生相关。     

The association of the apolipoprotein E gene promoter polymorphisms and haplotypes with serum lipid and lipoprotein concentrations

BACKGROUND: Apolipoprotein E (ApoE) is known to modulate lipoprotein transport and metabolism. The common APOE epsilon2/epsilon3/epsilon4 polymorphism explains part of the variation in plasma cholesterol levels. Polymorphisms of the APOE gene regulatory region are suggested to be involved in explaining variation of lipoprotein levels within the APOE epsilon2/epsilon3/epsilon4 genotypes. OBJECTIVES: To study the associations of the APOE gene promoter polymorphisms -219G/T and +113G/C and their haplotypes with serum lipid and lipoprotein concentrations, especially within the most common APOE epsilon3/epsilon3 genotype group. SUBJECTS AND METHODS: From 219 middle-aged Finnish men, APOE genotypes were determined and haplotypes estimated. Plasma lipoproteins were isolated by ultracentrifugation and their lipids were measured. RESULTS: The studied APOE promoter polymorphisms and haplotypes associated with certain lipid variables independently of the APOE epsilon2/epsilon3/epsilon4 genotype. Within the APOE epsilon3/epsilon3 group, both -219G/G and +113G/G genotypes associated statistically significantly with higher levels of very low-density lipoprotein (VLDL) cholesterol, apoB and triglycerides, and tended to associate with lower HDL-cholesterol concentrations than the other genotypes. Compared with the -219T/+113C/epsilon3 haplotype, the more common -219G/+113G/epsilon3 haplotype was found more frequently among the group having high (over median) VLDL-cholesterol and triglyceride concentrations (OR 2.6, p<0.001 and OR=2.1, p=0.009, respectively). CONCLUSIONS: In addition to the APOE epsilon2/epsilon3/epsilon4 polymorphism, the promoter polymorphisms -219G/T and +113G/C as well as their haplotype modulate lipid and lipoprotein concentrations in middle-aged Finnish men.     

Differences in frequency of the deletion polymorphism of the angiotensin-converting enzyme gene in different ethnic groups.

A polymorphism characterized by the insertion or deletion of a 287-bp Alu repeat sequence in intron 16 of the angiotensin-converting enzyme gene determines about half the serum angiotensin-converting enzyme level variability among individuals. The deletion polymorphism is associated with higher levels of angiotensin-converting enzyme and perhaps with a greater risk of cardiovascular diseases. The relative frequency of this genetic polymorphism in different ethnic groups is not known. The objective of this study was to compare the frequency of angiotensin-converting enzyme gene insertion/deletion polymorphism in different ethnic groups. Angiotensin-converting enzyme genotype was determined in middle-aged healthy hospital workers of three different ethnic origins (African Americans, whites, and Indians). There were 142 African Americans, 136 Indians, and 82 whites. The distribution of the deletion-deletion, insertion-deletion, and insertion-insertion genotypes in African Americans (29%, 60%, and 11%, respectively), Indians (19%, 50%, and 31%, respectively) and whites (29%, 40%, and 31%, respectively) was significantly different (p = < 0.005). The frequency of the deletion allele among African Americans, Indians, and whites (0.59, 0.49, and 0.44, respectively) was also significantly different (p=0.05). African Americans had the highest frequency of deletion allele and the lowest frequency of the insertion-insertion genotype among the three groups. The frequency of the deletion polymorphism of the angiotensin-converting enzyme gene is different among African Americans, whites, and Indians. This may be important in relation to the high risk of cardiovascular morbidity and mortality in African Americans and may be relevant in explaining differences in cardiovascular diseases in different populations. This finding also emphasizes the importance of studying angiotensin-converting enzyme gene polymorphism in genetically homogenous populations. Because of the small size of this study, however, these findings need further confirmation.     

Association of polymorphism in the promoter region of the apolipoprotein E gene with diastolic blood pressure in normotensive Japanese.

The epsilon4 allele of apolipoprotein E (APOE) is reported to be a genetic risk factor of atherosclerosis through hyperlipidemia and late-onset Alzheimer's dementia. A recent report showed that a genetic variant (A -491T) in the promoter region of the APOE gene increases the risk of Alzheimer's disease. In the present study, we examined whether these APOE polymorphisms were genetically involved in essential hypertension. Japanese hypertensives (n=180) with a family history of hypertension and normotensive controls (n=195, sex and age matched with hypertensives) were recruited from the outpatients of Osaka University Hospital, and an informed consent to participate in the study was obtained from each person. APOE polymorphisms were determined using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The frequencies of the A -491 allele in hypertensives and normotensives were 0.98 and 0.97, respectively, and the TT/-491 genotype was not found in either group. No significant differences between hypertensives and normotensives were observed in allele frequencies in either APOE polymorphism; however, the mean diastolic blood pressure in normotensive subjects with AA/-491 was significantly higher than in the subjects with AT/-491 (p < 0.01). These results suggest that the presence of the APOE promoter polymorphism is not a major risk factor for hypertension but that it does have some minor effect on basal blood pressure variation.     

醛固酮合成酶CYP11B2基因多态性与心脑血管病的研究进展

醛固酮合成酶是醛固酮合成过程中最后一步生化反应的催化酶,其编码基因为CYP11B2.醛固酮在心脑血管病的发生、发展中具有重要作用,CYP11B2基因-344T/C多态性与原发性高血压、缺血性心脏病及缺血性脑血管病密切相关.     

Interleukin 6-174 G/C promoter gene polymorphism in centenarians: no evidence of association with human longevity or interaction with apolipoprotein E alleles

The C allele at position -174 in the promoter of the interleukin 6 (IL-6) gene has been associated with reduced gene expression and reduced plasma levels of IL-6. Given that IL-6 tracks with functional disability and age-related diseases, there may be attrition or reduction in the frequency of the homozygous subjects, who produce higher IL-6 serum levels, in older survivors in a population. In fact, a marked reduction of the IL-6*G/*G genotype was recently demonstrated in male though not female Italian centenarians compared with younger age groups. First aim of the present study was to investigate whether there was evidence of an association among IL-6 -174 G/C promoter polymorphism and extreme longevity in a population of 81 centenarians compared with a control group of 122 middle-aged healthy subjects (mean age: 51+/-18 SD; range: 19-73 years), from Apulia (Southern Italy). Secondly, we also tested possible interaction of apolipoprotein E (APOE) alleles with the IL-6 -174 G/C promoter polymorphism in view of our recent findings for reduced APOE epsilon4 allele in centenarians. No differences have been found in the IL-6 -174 G/C promoter allele and genotype frequencies between centenarians and controls nor was there any observed interaction with APOE alleles that are also reputed to be linked to longevity. Regional genetic differences in conjunction with differing environmental factors may explain in part previous results suggesting a role of this polymorphism in longevity.