Apolipoprotein E genotypes in offspring with a positive and negative family history of premature myocardial infarction

Apolipoprotein E (apo-E) aliele and genotype frequencies were evaluated in offspring with positive (MI-offspring) and negative (control-offspring) parental history of myocardial infarction (MI). The apo-E allele frequencies in MI-and control-offspring were as follows: ε2: 9.04 and 2.08% (p < 0.02), ε3: 84.04 and 87.5%. ε4: 6.91 and 10.41%, respectively. The frequencies of the E2-genotypes were significantly lower in offspring of controls (4.2%, 17.0%, respectively, p < 0.03). The ε2-allele is associated with raised plasma triglyceride concentrations in subjects on a diet high in saturated fat. We therefore hypothesize that offspring carrying an ε2-allele are predisposed to develop disturbance of plasma triglyceride metabolism when exposed to a traditional Slovak high-fat diet and/or weight gain, resulting in altered lipid levels and increased predisposition to atherosclerosis.     

Apolipoprotein E5 and E7 in apparently healthy Japanese males: Frequencies and relation to plasma lipid levels

Summary In order to determine the frequencies of apolipoproteins (apo) E5 and E7 and their relation to plasma lipid levels, apo E phenotypes were determined in 608 healthy Japanese male adults by two-dimensional gel electrophoresis. Apo E5 and E7 were observed in 2.8% of the subjects, in addition to the three common apo E isoforms, E2, E3, and E4. Apo E5 was divided into two subtypes based on the migration rate on SDS/PAGE, E5f is the type with faster migration and E5s slower migration. The gene frequencies were: the 3 allele, 0.841; the 4 allele, 0.095; the 2 allele, 0.049; the 7 allele, 0.009; the 5 allele encoding apo E5f (the 5f allele), 0.004; and the 5 allele encoding apo E5s (the 5s allele), 0.001. The five individuals with apo E5f and the eleven with apo E7 were heterozygotes and normocholesterolemic. Also plasma apo B and apo E levels were not increased in any subjects with apo E5f or apo E7. The data suggests that apo E5f and E7 are not rare in the Japanese population but that neither apo E5f nor E7 are associated with hypercholesterolemia in most of the heterozygotes.     

Apolipoprotein E polymorphism in the Greek population

The APOE gene is located on chromosome 19, and the three common alleles are designated ε2, ε3, and ε4. The ε4 allele is associated with increased plasma cholesterol, atherosclerosis and cardiovascular disease, Alzheimer's disease, and decreased longevity. The objective of the present study was to estimate the distribution of APOE alleles in the Greek population by DNA analysis. The material consisted of 216 voluntary, healthy Greek blood donors (146 males/70 females). The APOE allele frequencies were ε2: 5.3%, ε3: 88.2%, ε4: 6.5%. The ε4 allele frequency of 6.5% in the Greek population is, together with the frequency in the Chinese population, among the lowest in the world.     

载脂蛋白E基因多态性与早发冠心病的关系及其对血脂的影响

目的 研究载脂蛋白E（apolipoprotein E,apoE)基因多态性与早发冠心病（coronary heart disease,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（polymerase chain reaction-restricted fragment hength polymorphism,PCR-RFLP)基因分析方法,测定52例早发CHD、161例迟发CHD患者和180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、E4／4、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＜0．01）;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为高（P＜0．05）。apoE各等位基因型之间,TC和LDL－C水平之间存在统计学差异（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。     

2型糖尿病患者载脂蛋白e4等位基因与颈动脉中内膜厚度的关系

目的：了解2型糖尿病（diabetes mellitus,DM)患者载脂蛋白E（apolipoprotein E,apoE)基因型与颈动脉中内膜厚度的关系。方法：选择255例无血管并发症的2型DM患者和107名健康个体，采用聚合酶链反应等位基因特异寡核苷酸探针杂交技术检测其apoE基因型。结果：2型DM组与对照组apoE基因型及等位频率差异无显著性（P＞0．05）；两组中e4/4、e4/3亚组总胆固醇、低密度脂蛋白胆固醇、脂蛋白（a)水平明显高于e3/2、e2/2亚组（P＜0．05）；两组中e4/4、e4/3亚组颈动脉中内膜厚度明显高于e3/2,e2/2亚组（P＜0．05）。不论在对照组还是在2型DM ，当调整总胆固醇、低密度脂蛋白胆固醇、甘油三酯、脂蛋白（a)、血糖、年龄、体重指数、吸烟等因素的影响后，协方差分析结果显示，颈动脉中内膜厚度在这两个基因型亚组喑差异有显著性（P＜0．05）。结论：不论在健康人还是在2型DM患者，e4等位基因与早期颈动脉粥样硬化关联。     

载脂蛋白B基因C7673T多态与有家族聚集现象脑出血的关系

目的 探讨载脂蛋白B基因(apolipoprotein B,apo B)C7673T多态与长沙地区汉族人群有家族聚集现象脑出血的关系.方法 采用聚合酶链反应-限制性片段长度多态性分析法和DNA直接测序法检测长沙地区汉族15个有家族聚集现象脑出血家系117名成员、93例散发脑出血患者和100名正常对照者的apoB基因C7673T多态;氧化酶法测定血清甘油三酯、总胆固醇、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇水平,酶联免疫吸附法测定脂蛋白(a)浓度,免疫比浊法测定apoB100及apoA Ⅰ浓度.结果 (1)家系组脑出血患者组及其Ⅰ、Ⅱ、Ⅲ级亲属组、散发脑出血组和对照组apoB基因C7673T多态T等位基因频率分别为0.176、0.136、0.058、0.048、0.081、0.040.(2)家系组脑出血患者组及其Ⅰ级亲属组apoB基因C7673T多态T等位基因频率显著高于对照组(P＜0.01,P＜0.01),而家系组Ⅱ、Ⅲ级亲属组与对照组相比差异无统计学意义(P＞0.05);家系组脑出血患者组apoB基因C7673T多态T等位基因频率显著高于散发脑出血组(P＜0.05).(3)家系组脑出血患者组及散发脑出血组中,apoB基因C7673T多态TC基因型较CC基因型的总胆固醇、低密度脂蛋白胆固醇显著增高,而高密度脂蛋白胆固醇显著降低(P＜0.05),其它指标差异无统计学意义(P＞0.05).结论 apoB基因C7673T多态T等位基因可能与长沙地区汉族人群有家族聚集现象脑出血有关;apoB基因C7673T多态T等位基因可能通过改变血脂水平影响脑出血的发生发展.     

Apolipoprotein E gene polymorphism in cerebrovascular disease: a case-control study

The association between apolipoprotein E (apo E) polymorphism and stroke has been controversial. So far there are no studies reported on the polymorphism of apolipoprotein E in cerebrovascular diseases in the Asian Indians. A blinded case-control study was therefore undertaken and the apo E genotypes and lipid profile of a total of 120 subjects (63 stroke patients and 57 healthy controls) were done. The frequency distribution of apo E alleles and genotypes were assessed and their relation with the occurrence of stroke in Asian Indian subjects was determined. A significantly high frequency of apo epsilon4 allele (30%) was observed in the stroke patients than the controls (11%) (p < 0.005), and patients with epsilon4 allele had a fourfold higher odds to develop stroke OR (95%CI) 4.2 (1.8-10.1) (p < 0.005). On multivariate analysis, after adjusting for age, triglycerides and hypertension, the association of epsilon4 allele with stroke was found to be no longer statistically significant, OR (95%CI) 1.2 (0.4-4.5) (p = NS). On multiple logistic regression analysis age, OR (95%CI) 1.1 (1.1-1.2) (p < 0.001), and hypertension OR (95%CI) 15.1 (2.6-89.1) (p < 0.005) were found to be independent risk factors for development of stroke. This is the first report to have examined the association of apo E gene polymorphism with stroke in the Asian Indians. This study suggests that apo epsilon4 allele, triglycerides, age and hypertension are the predictors for stroke development.     

单克隆抗体在载脂蛋白E多态性研究中的应用

应用制备的抗人血清载脂蛋白E单克隆抗体作为一抗,通过微量脱脂血清等电聚焦电泳及免疫印迹的方法分析了载脂蛋白E表型及其多态性。本法与常规法比较。不需要超速离心分离人血清VLDL的过程,而且仅需微量血清,便于临床应用。采用本法作者分析了94例正常人载脂蛋白E表型多态性,从中检出5种表型,以E3/3表型多见(70.21％)。31份血清同时用本法和常观法测定,所得结果一致。本文研究表明,单克隆抗体在载脂蛋白E多态性研究方面具有重要实用价值。     

Analysis of the potential role of Apolipoprotein E polymorphism in genetic predisposition to spontaneous abortion

Citation Rynekrova J, Kasparova D, Adamkova V, Fait T, Hubacek JA. Analysis of the potential role of apolipoprotein E polymorphism in genetic predisposition to spontaneous abortion. Am J Reprod Immunol 2012; 67: 179–183 Problem Up to 20% of pregnancies end in the first trimester by spontaneous abortion, but a significant number remains unexplained. The aim of this study is to investigate the role of variants within the gene for apolipoprotein E (APOE) in the genetic determination of spontaneous abortions. Method of study We collected DNA from 410 tissue samples of spontaneous abortions, and APOE was genotyped by PCR–RFLP method. The frequencies were compared with a population sample of adults (N = 2606) and with a positive control (1060 women with at least two children). Results The frequencies of the APOE genotypes in abortions (APOE2E2 + E3E2 = 0.132; APOE3E3 = 0.661; APOE3E4 + E4E4 = 0.195; APOE4E2 = 0.012) did not significantly differ (P = 0.604) from the frequencies in analyzed adult population study (APOE2E2 + E3E2 = 0.132; APOE3E3 = 0.686; APOE3E4 + E4E4 = 0.169; APOE4E2 = 0.014) or from the positive control (APOE2E2 + E3E2 = 0.133; APOE3E3 = 0.691; APOE3E4 + E4E4 =0.166; APOE4E2 = 0.010; P = 0.592). Conclusion Our study suggests that APOE may not be associated with spontaneous abortions in Caucasians.     

The effects of age,gender, and family history on blood pressure of normotensive college students

Offspring with a parental history of hypertension are, by some estimates, four times more likely to develop the disease (Corvol et al., 1992). While some studies suggest that an increased risk is observable in eight year old children, others suggest that the increased risk does not become apparent until age 20. This study examined this discrepancy by screening resting blood pressures from 403 young adults. After adjusting for body mass, a significant family history × age × gender interaction (p<.01) suggests that the effect of family history on systolic blood pressure varies by age and gender. The influence of positive family history becomes apparent in males by age 20 and in females by age 22. This relationship may help provide a rationale for interpretation and reconciliation of disparate results in the literature, and clarify our understanding of the etiologic mechanisms responsible for development of essential hypertension.     

A polymorphism in the promoter of UCP2 gene modulates lipid levels in patients with type 2 diabetes

A G/A single nucleotide polymorphism (SNP) in the position -866 of the UCP2 promoter modulates UCP2 expression in adipose tissue and pancreatic beta-cell, and is associated with variations of body mass index (BMI) and insulin secretion in nondiabetic subjects. We investigated associations of this SNP with traits related to obesity, dyslipidemia, and hyperglycemia in patients with type 2 diabetes. The -866 G/A SNP in the UCP2 promoter was genotyped by PCR/RFLP in 681 type 2 diabetic patients. Increased triglyceride (> or = 1.70 mM), total cholesterol (> or = 6.0 mM) and LDL-cholesterol (> or = 3.35 mM) levels were significantly less frequent in homozygous carriers of the G-allele than in homozygous carriers of the A-allele. Odds ratios for the risk of dyslipidemia in GG vs AA carriers were 0.45, 0.57, and 0.50, for triglyceride, total cholesterol and LDL-cholesterol, respectively (all p<0.007). No genetic effects of this polymorphism on the BMI or on traits related to the severity of hyperglycemia were observed. In conclusion, a common polymorphism in the promoter region of the UCP2 gene modulates triglycerides and cholesterol levels in French Caucasian subjects with type 2 diabetes. The implications of this effect in the evolution of type 2 diabetes and its macrovascular complications deserve to be investigated.     

apoH基因多态性与脑卒中的相关性研究及其对血脂的影响

目的：探讨载脂蛋白H（apolipoprotein H,apoH）基因第8外显子G1025C（Try316Ser）多态性与长沙地区汉族人脑卒中的关系及其对血 脂的影响。方法：采用PCR－单链构象多态技术和DNA直接测序法检测长沙地区汉族260例脑卒中患者、20个脑卒中家系成员和100名健康对照者的apoH基因第8外显子G1025C（Try316Ser）多态性；酶联免疫吸附法检测抗磷脂抗体水平；酶法测定总胆固醇（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），免疫比浊法测定apoA-I及apo B100，酶联免疫吸附法测定脂蛋白a血清水平。结果：长沙地区汉族人apoH基因G1025C（Try316Ser）多态存在GG、GC两种基因型，脑卒中组及其各亚组G1025C（Try316Ser）多态基因频率分布与对照组比较差异无显著性（P＞0．05）；分析不同基因型对血脂、脂蛋白水平的影响，发现脑梗塞组和对照组GC基因型血清TG水平均明显高于GG基因型（P＜0．05）。结论：长沙地区汉族人apoH基因G1025C（Try316Ser）多态性可能与脑卒中的易患性无关，但与血脂代谢有一定关联。     

脂联素多聚体及基因多态性与2型糖尿病

脂联素是新近发现的脂肪细胞分泌的特异性细胞因子,在机体糖和脂肪代谢、维持能量平衡过程中发挥重要作用。正常人脂联素基因序列中存在相当数量的等位基因单核苷酸多态性(SNPs),其中5′侧翼区-11377(C/G)和外显子2 45(T/G)遗传多态性与脂联素血浆水平以及与肥胖、2型糖尿病(type 2 d iabetes m ellitus,T2DM)和冠状动脉粥样硬化有关。脂联素在血浆中以高分子量(h igh molecu lar we ight,HMW)的多聚体和低分子量(low molecu lar we ight,LMW)的六聚体2种形式存在。HMW脂联素增加与胰岛素敏感性呈正相关,LMW脂联素的功能需要进一步探讨研究。     

Effect of the APOE‐491A/T promoter polymorphism on apolipoprotein E levels and risk of Alzheimer disease: The Rotterdam Study

The apolipoprotein E (APOE) gene is involved in lipid transport. A common polymorphism in this gene with the APOE*2, APOE*3, and APOE*4 alleles influences plasma levels of apolipoprotein E and cholesterol. Besides its role in lipid transport, the APOE*4 allele is a genetic risk factor for Alzheimer disease (AD). Recently, a polymorphism in the APOE promoter region was found to be involved in plasma apolipoprotein E levels and was found associated with AD. We studied the effect of this ?491A/T promoter polymorphism on plasma apolipoprotein E levels and risk for AD in a population‐based case‐control study. We found that there was a modest but statistically significant effect of the ?491A/T polymorphism on plasma apolipoprotein E levels independent of the APOE genotype. The lowest plasma levels were measured for the AA genotype, highest levels for the TT genotype, and intermediate levels for the heterozygotes. There was a small effect of the ?491 AA genotype on AD risk that disappeared after adjusting for APOE genotypes. Our data suggest that the ?491A/T polymorphism has an APOE genotype‐independent effect on plasma apolipoprotein E levels but no APOE‐independent effect on AD risk. © 2002 Wiley‐Liss, Inc.     

Apolipoprotein E polymorphism is not associated with lipid levels and coronary artery disease in Greek patients with familial hypercholesterolaemia

Abstract Familial hypercholesterolaemia is a genetic disorder characterised by high low-density lipoprotein (LDL) cholesterol concentrations, which frequently gives rise to premature coronary artery disease (CAD). The clinical expression of familial hypercholesterolaemia is highly variable even in patients carrying the same LDL receptor gene mutation. This variability may be due to environmental and other genetic factors. Apolipoprotein E (Apo-E) has been extensively studied for its effects on the phenotype of familial hypercholesterolaemia. In this study we examined the influence of Apo-E genotype on lipid parameters and the incidence of CAD in 93 Greek patients with familial hypercholesterolaemia. Apo-E E2, E3 and E4 allele frequencies were 0.06, 0.86 and 0.09 respectively. The levels of total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, apolipoproteins A and B and lipoprotein α did not differ significantly among carriers and non-carriers of the E4 allele. The prevalence of CAD and hypertension did not differ either. Our results suggest that the E4 allele is not associated with lipid levels or with the prevalence of CAD among familial hypercholesterolaemia patients of the Greek population. *The two authors were equally involved in the work     

The effect of the apolipoprotein E polymorphism on lipid levels in patients with familial defective apolipoprotein B-100

Summary Serum lipid concentrations of patients with familial defective apolipoprotein B-100 (FDB) show a high interindividual variability although the underlying defect is caused by a single point mutation. On the other hand, several genetic factors modulating serum cholesterol levels are known, such as DNA polymorphisms of the apopolipoprotein B or the apolipoprotein E (apo E) gene. To assess the effect of the apo E polymorphism on serum cholesterol, lipid levels of FDB patients (n=36) were compared with those of a normolipidemic control group (n=272) according to their apo E genotype. For the FDB group mean values of low-density lipoprotein (LDL) cholesterol (mg/dl) were 225.7 ± 53.7 for E3/2 genotype (n = 3), 234.2±48.3 for E3/3 genotype (n=20), and 252.4±73.8 for E4/3 genotype (n=13). Means of triglycerides (mg/dl) were 121.0±21.2, 114.8± 60.7, and 110.0 ± 62.8 for the respective apo E genotypes. The calculated average effect of the apo E alleles on LDL cholesterol levels was –6.0% for allele e2 and +3.7% for e4 relative to the whole FDB group. The effect on triglyceride levels was +7.5% for e2 and –3.6% for e4. The control group showed a similar variation in LDL cholesterol depending on the different apo E genotypes. About 6% of the total variation in LDL cholesterol can be accounted for by the apo E locus in normolipidemic and hypercholesterolemic individuals alike.Abbreviations FDB familial defective apolipoprotein B-100 - apo apolipoprotein - LDL low-density lipoprotein - VLDL very low density lipoprotein - HDL high-density lipoprotein - PCR polymerase chain reaction Dedicated to Prof. Dr. N. Zöllner on the occasion of his 70th birthday     

Intercellular adhesion molecule-1 (ICAM-1) K469E polymorphism: no association with type 1 diabetes among Finns

The intercellular adhesion molecule-1 (ICAM-1) has an important role in the process of lymphocyte migration and activation, and is supposed to be involved in the pathogenesis of type 1 diabetes. We studied A/G (K469E) polymorphism of the ICAM-1 gene in 218 type 1 diabetes patients and 212 controls from Finland and found no association. We then studied transmission of the ICAM-1 alleles in 102 Finnish families using a transmission disequilibrium test (TDT). Alleles A and G were transmitted to the affected offspring in 50% each. Stratification by the HLA-DQB1-DQA1 genotypes, sex and age at onset did not reveal association. Our data demonstrate that in the Finnish population K469E polymorphism of the ICAM-1 gene is not associated with type 1 diabetes.     

阿尔茨海默病与载脂蛋白E基因-427C/T多态性的关联研究

目的 探讨上海地区汉族人群载脂蛋白E(apolipoprotein E，apoE)基因启动子区—427C／T多态性与Alzheimer病(Alzheimer's disease，AD)发病风险的关系。方法 采用聚合酶链反应和限制性片段长度多态性方法，在104例AD患者和110名正常人中检测了apoE基因—427C／T各基因型及基因频率的分布。按比值比(odds ratio，0R)作疾病关联分析。结果 (1)AD患者与正常对照人群之间不存在—427C／T各等位基因和基因型频率分布的差异(P＞0．05)；(2)按apoE ε4基因分层后，无论是ε4型人群还是非ε4人群都不存在AD患者与正常老人间多态分布的差异(P＞0．05)；(3)在—427C／T 3种基因型中，仅T／T型AD与apoE ε4等位基因呈正关联(OR＝3．94，95％CI：2．206—7．038，x^2＝21．48，P＜0．05)。结论 上海地区汉族人群中，apo E基因—427C／T多态不是AD的疾病易感因子。     

Association of FADS2 rs174575 gene polymorphism and insulin resistance in type 2 diabetes mellitus

BackgroundMany risk factors contribute to the pathogenesis of diabetes. Gene and lifestyle factors are considered to be the major contributors. A dietary pattern is attributed to be one of the lifestyle risk factors favoring diabetes. The present study aims to find an association between fatty acid desaturase (FADS) gene polymorphism and glycemic profile in type 2 diabetes mellitus (T2DM).MethodologyA total of 429 subjects were included in the study on the basis of inclusion and exclusion criteria, of which 213 and 216 subjects were diabetic and control, respectively. Body mass index was calculated. Fasting plasma glucose, glycated hemoglobin (HbA1c) and insulin were measured using commercially available kits. rs174575 of FADS2 was selected based on previous publications and identified using the dbSNP database. To compare the biochemical parameters with the genotype, the following three models were used: additive model (CC vs CG vs GG), dominant model (CC + CG vs GG), and recessive model (CC vs CG + GG).Results and DiscussionFBS, HbA1c, insulin, HOMA-IR, and HOMA-B exhibited a high and statistically significant difference between subjects and controls. The three models exhibited a statistically significant difference between FBS, HOMA-IR, and HOMA- B (p<0.05).ConclusionThe distribution of rs174575 genotype differed significantly between the subjects and controls in the present study. The study revealed that genetic variation in FADS2 is an additional facet to consider while studying the risk factors of T2DM.