Is the ApoE polymorphism associated with dilated cardiomyopathy?

Apolipoprotein E (ApoE) is 34 kDa protein involved in the modulation of cholesterol transport and homeostasis. Polymorphism of the ApoE gene has been implicated in many chronic cardiovascular and neuronal diseases. ApoE epsilon4 allele has been reported to be associated with increased risk of cardiovascular diseases such as myocardial infarction, hypertension, coronary heart disease, etc. Fifty patients with the end-stage dilated cardiomyopathy (DCM) and advanced congestive heart failure were examined in our study. For evaluation of ApoE polymorphism, novel approach of fast screening of ApoE gene polymorphism by combination of PCR and blotting (CVD StripAssay) was used. Individual genotypes were correlated with basic cardiologic clinical parameters. The reported frequency of this allele in Caucasian population is 14.7 %. Our results showed that in patients with DCM frequency of the ApoE epsilon4 allele is 40 %. Frequency of the genotype epsilon2/4 was 58 % and epsilon3/4 was 22 %. Comparison with control Caucasian groups monitored by others clearly revealed that frequency of epsilon4 alelle is increased in patients with advanced stages of DCM. This observation suggests association of ApoE polymorphism with severe form of DCM. Physiological consequences of this observation remain to be clarified.     

Apolipoprotein E deficiency promotes increased oxidative stress and compensatory increases in antioxidants in brain tissue

The epsilon 4 allele of the apolipoprotein E gene (ApoE) is associated with Alzheimer's disease (AD). The extent of oxidative damage in AD brains correlates with the presence of the E4 allele of ApoE, suggesting an association between the ApoE4 genotype and oxygen-mediated damage in AD. We tested this hypothesis by subjecting normal and transgenic mice lacking ApoE to oxidative stress by folate deprivation and/or excess dietary iron. Brain tissue of ApoE-deficient mice displayed increased glutathione and antioxidant levels, consistent with attempts to compensate for the lack of ApoE. Folate deprivation and iron challenge individually increased glutathione and antioxidant levels in both normal and ApoE-deficient brain tissue. However, combined treatment with folate deprivation and dietary iron depleted antioxidant capacity and induced oxidative damage in ApoE-deficient brains despite increased glutathione, indicating an inability to compensate for the lack of ApoE under these conditions. These data support the hypothesis that ApoE deficiency is associated with oxidative damage, and demonstrate a combinatorial influence of genetic predisposition, dietary deficiency, and oxidative stress on oxidative damage relevant to AD.     

载脂蛋白E基因多态性与2型 糖尿病脑梗死的关系

研究载脂蛋白E (ApoE) 基因多态性与中国东北汉族2型糖尿病合并脑梗死的关系。采用聚合酶链反应－限制性片段长度多态性（PCR-RFLP）技术,检测了208例个体的ApoE基因多态性,其中对照（CON）组69例,2型糖尿病无大血管病变（T2DM）组67例和2型糖尿病合并脑梗死（T2DMCI）组72例;同时测定了其中70例T2DMCI患者的血脂含量。CON组等位基因频率为：ε2 9.6％、ε3 82.4％、ε4 8.1％,基因型频率为：ε2ε3 13.2％、ε3ε367.6％、ε3ε416.2％;T2DM组等位基因频率为：ε2 10.5％、ε3 84.3％、ε4 5.2％,基因型频率为：ε2ε3 19.4％、ε3ε370.1％、ε3ε49％;T2DMCI组等位基因频率为：ε2 11.8％、ε3 84.7％、ε4 3.5％,基因型频率为：ε2ε3 15.2％、ε3ε375％、ε3ε44.2％。3组间等位基因和基因型频率的差异经检验无统计学意义。T2DMCI患者中各基因型之间的血浆总胆固醇 （TC）、甘油三酯 （TG）、高密度脂蛋白胆固醇（HDL-C）和低密度脂蛋白胆固醇（LDL-C）水平亦无显著性差异。在中国东北汉族人群中,未发现ApoE基因多态性与T2DMCI之间存在关联,亦未发现ApoE基因多态性与T2DMCI患者的TC、TG、 HDL-C和 LDL-C水平之间存在关联。Abstract: In order to explore the association of apolipoprotein E (ApoE) gene polymorphism with cerebral infarction in type 2 diabetic patients of Han nationality in Northeast China , the genotypes of ApoE gene were analyzed by polymerase chain reaction –restriction fragment length polymorphism (PCR-RFLP) in the 208 cases, including 69 cases in control (CON) group and 67 in type 2 diabetes mellitus (T2DM) group as well as 72 in type 2 diabetes mellitus with cerebral infarction (T2DMCI) group. Plasma lipid content in T2DMCI was also detected for 70 cases. The distribution of genotypes in ApoE gene,ε2ε3、ε3ε3 as well asε3ε4 was no significant difference in three groups (ε2ε3 : 13.2％、ε3ε3 : 67.6％、ε3ε4 : 16.2％in CON group;ε2ε3 : 19.4％、ε3ε3: : 70.1％ε3ε4 : 9％in T2DM group;ε2ε3 : 15.2％、ε3ε3 : 75％、ε3ε4 : 4.2％in T2DMCI group).The allele frequencies ofε2、ε3 andε4 were not significantly different in the three groups, either (ε2 : 9.6％、ε3 : 82.4％、ε4 : 8.1％in CON group; ε2 :10.5％、ε3 :84.3％、ε4 : 5.2％in T2DM group; ε2 :11.8％、ε3 :84.7％、ε4 : 3.5％in T2DMCI group). The levels of total cholesterol (TC), tryglyceride (TG), high density lipoprotein-cholesterol (HDL-C) and low density lipoprotein-cholesterol (LDL-C) were not significantly different among the different genotypes in T2DMCI group. The study confirmed that the polymorphisms of ApoE gene are neither associated with the T2DMCI, nor with the levels of plasma lipid in T2DMCI.     

Apolipoprotein E polymorphism in the Finnish population: gene frequencies and relation to lipoprotein concentrations

ApoE phenotypes were determined in 615 unrelated Finnish individuals. The apoE gene frequencies observed (epsilon 2, 0.041; epsilon 3, 0.733; epsilon 4, 0.227) differ significantly from those in other populations. The frequency of the allele epsilon 2 was lower and that of epsilon 4 higher than in all other studied populations. Plasma lipids and apolipoproteins A-I, A-II and B were recorded in 207 of the typed subjects. By comparison with the most frequent homozygous apoE 3/3 phenotype, it was found that total cholesterol, LDL-cholesterol, and apoB concentrations were all markedly higher in apoE 4/4 and to a lesser degree in apoE 4/3 phenotypic groups. On the other hand, these lipid and apolipoprotein levels tended to be lower in E-2 heterozygotes. These data confirm and extend, in a different ethnic group, previous results of an effect of apoE genes on plasma lipoprotein concentrations. The data suggest that the apoE gene locus may be one factor responsible for the high LDL cholesterol concentrations in the Finnish population.     

Ageing related thyroid deficiency increases brain-targeted transport of liver-derived ApoE4-laden exosomes leading to cognitive impairment

Alzheimer’s disease (AD) is the prevalent cause of dementia in the ageing world population. Apolipoprotein E4 (ApoE4) allele is the key genetic risk factor for AD, although the mechanisms linking ApoE4 with neurocognitive impairments and aberrant metabolism remains to be fully characterised. We discovered a significant increase in the ApoE4 content of serum exosomes in old healthy subjects and AD patients carrying ApoE4 allele as compared with healthy adults. Elevated exosomal ApoE4 demonstrated significant inverse correlation with serum level of thyroid hormones and cognitive function. We analysed effects of ApoE4-containing peripheral exosomes on neural cells and neurological outputs in aged or thyroidectomised young mice. Ageing-associated hypothyroidism as well as acute thyroidectomy augmented transport of liver-derived ApoE4 reach exosomes into the brain, where ApoE4 activated nucleotide-binding oligomerisation domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome by increasing cholesterol level in neural cells. This, in turn, affected cognition, locomotion and mood. Our study reveals pathological potential of exosomes-mediated relocation of ApoE4 from the periphery to the brain, this process can represent potential therapeutic target.Subject terms: Cognitive neuroscience, Alzheimer''s disease, Cellular neuroscience     

Protective effect of apolipoprotein E2 on coronary artery disease in African Americans is mediated through lipoprotein cholesterol

We studied the relationship of apolipoprotein E (apoE) isoforms and coronary artery disease (CAD) in 224 African Americans and 326 Caucasians undergoing diagnostic coronary angiography. The presence of CAD was defined as >50% stenosis in at least one artery. ApoE allele frequencies were 0.12, 0.62, and 0.26 for epsilon 2, epsilon 3, and epsilon 4, respectively, in African Americans and 0.08, 0.78, and 0.14 for epsilon 2, epsilon 3, and epsilon 4, respectively, in Caucasians. Among African Americans, CAD was present in 9 of 34 epsilon 2 carriers (26%), significantly smaller (P < 0.05) in proportion compared with 39 of 82 epsilon 3 carriers and 43 of 92 epsilon 4 carriers (48% and 47%, respectively), suggesting a protective effect of the epsilon 2 allele. No such difference was seen in Caucasians. In African Americans but not Caucasians, LDL cholesterol was lower in epsilon 2 carriers than in epsilon 3 and epsilon 4 carriers (106 vs. 127 and 134 mg/dl, respectively; P < 0.005). After adjusting for lipid levels, the association between apoE2 and CAD was no longer significant. Thus, the protective effect of apoE2 seen in African Americans could be explained by a favorable lipid profile in epsilon 2 carriers, whereas in Caucasians, the absence of such a protective effect could be attributable to the lack of effect of apoE2 on the lipid profile.     

Polymorphism of the apolipoprotein E gene and the risk of myocardial infarction

The apolipoprotein E (ApoE) gene polymorphism resulting from nucleotide substitutions in exon 4 was analyzed in Russian and Tatar patients with myocardial infarction (MI) from Bashkortostan. Alleles epsilon 2, epsilon 3, and epsilon 4 were identified by PCR. The genotype frequency distribution proved to be age-dependent in healthy Russians, genotype E2/3 increasing in frequency in subjects beyond 45. Russians who suffered MI under 45 had lower frequencies of genotype E3/3 (50.00% vs. 75.47% in controls of the same age, P = 0.013, OR = 0.33) and allele epsilon 3 (72.12% vs. 85.85%, P = 0.020, OR = 0.43) and a higher frequency of allele epsilon 4 (22.12% vs. 10.38%, P = 0.030, OR = 2.45). Russians who suffered MI complicated by cardiogenic shock (CS) had a significantly higher frequency of genotype E3/4 and lower frequencies of genotype E3/3 and allele epsilon 3 as compared with MI patients without CS. In Tatars, genotype E4/4 occurred at a frequency of 14.29% in patients who suffered MI under 45, and was not detected in healthy subjects of the same age (P = 0.024, OR = 17.85). Thus, the ApoE polymorphism was associated with higher risk of MI in Russians and Tatars under 45.     

Apolipoprotein E gene polymorphism,hypercholesterolemia and glomerular filtration rate in type 2 diabetic subjects: A 9-year follow-up study

OBJECTIVE: To study the association between apolipoprotein E (apoE) genotype and the rate of decline in glomerular filtration rate (GFR) in type 2 diabetic patients in a 9-year prospective study. METHODS: GFR was determined in 84 type 2 diabetic patients by plasma clearance of (51)Cr-EDTA at baseline and after 9 years of follow-up. ApoE genotypes were determined by polymerase chain reaction and restriction enzyme HHAI digestion and designated as epsilon4 allele group (apoE4/2, 4/3 and 4/4 genotypes; n = 20) and non-epsilon4 allele group (apoE3/3 and E3/2 genotypes; n = 64). We focused our analysis on those patients who were more likely to progress to diabetic renal disease, i.e. whose GFR fell more than expected in the normal course of ageing [1 ml x min(-1) x (1.73 m(2))(-1) per year]. RESULTS: In the whole population, the decline in the GFR did not differ statistically significantly between the apoE genotype groups [p = 0.65 with analysis of variance for repeated variables (RANOVA) for interaction between apoE genotype group and time point]. However, among patients whose GFR changed more than 9 ml x min(-1) x (1.73 m(2))(-1), GFR showed a statistically significantly greater decline in the epsilon4 allele group (n = 11) than in the non-epsilon4 allele group (n = 43) [from 116 +/- 36 to 80 +/- 29 ml x min(-1) x (1.73 m(2))(-1) vs. from 119 +/- 20 to 96 +/- 18 ml x min(-1) x (1.73 m(2))(-1); p = 0.005 with RANOVA]. CONCLUSION: ApoE allele epsilon4 may speed up the rate of decline of the GFR in patients with progressive diabetic renal disease.     

Guidelines for treating epilepsy in the age of felbamate,vigabatrin, lamotrigine,and gabapentin.

For the first time in 15 years, new antiepileptic medications are available for the treatment of patients with seizure disorders. These drugs have demonstrated efficacy in animal models of epilepsy and in controlled clinical trials. Felbamate was licensed in 1993 for use as adjunctive therapy or monotherapy in adults with partial or tonic-clonic seizures and as adjunctive therapy for children with the Lennox-Gastaut syndrome. Gabapentin was approved January 1994 as adjunctive therapy in patients 12 years or older with partial seizures, with or without secondary generalization. Lamotrigine is expected to be approved this year for the treatment of partial and tonic-clonic seizures in adults. Last, a new drug application has been filed for vigabatrin this year, with possible licensing next year. These four anticonvulsants present new options in the treatment of patients with refractory epilepsy and are not merely congeners of previously available treatments. They have unique clinical spectrums and are reported to be safer and better tolerated than conventional therapy. Trials to compare their use with that of conventional therapy have not been done, and their use in the initial treatment of patients with epilepsy is not completely clear.     

Effects of apolipoprotein E genotype on blood lipid composition and membrane platelet fluidity in Alzheimer's disease.

The blood lipid composition (plasma, platelets and leukocytes), platelet membrane fluidity, apolipoproteins A and B in the plasma of AD patients and control subjects with distinct Apo E genotypes were investigated. No significant differences were found between the Apo E genotype and the cholesterol, phospholipids, triglycerides and Apo B levels in the plasma; cholesterol and phospholipids levels in platelet and leukocyte membranes; and platelet membrane fluidity of AD and control groups. However, the phospholipid levels in the leukocyte membranes of the control subgroup with the genotypes epsilon3/epsilon3 and epsilon3/epsilon4 and the AD subgroups with the genotypes epsilon2/epsilon3 and epsilon3/epsilon3, epsilon3/epsilon4 and epsilon4/epsilon4 were significantly lower than those observed in the control subgroup with the genotype epsilon2/epsilon3. Moreover, the cholesterol and phospholipid levels in the platelet membranes of the AD subgroup with the epsilon2 allele were significantly higher than those in the AD subgroup without the epsilon2 allele and the control subgroups with and without the epsilon2 allele. A strong correlation was found between cholesterol and phospholipids levels in the platelet membranes of the AD and control subgroups without the epsilon2 allele, but the residual cholesterol level in the platelet membranes of the AD subgroup was twice that observed in the control subgroup. Furthermore, the Apo A levels in the plasma of the AD subgroup with the epsilon3 allele were significantly lower than those observed in the AD subgroup without the epsilon3 allele and the control subgroup with the epsilon3 allele. The results are discussed in terms of involvement of lipid metabolism in the etiopathogenesis of AD.     

Apolipoprotein E phenotypes in Finnish youths: a cross-sectional and 6-year follow-up study

Apolipoprotein E (apoE) polymorphism is a genetic determinant of plasma lipid levels and of coronary heart disease (CHD) risk. We determined the apoE phenotypes and plasma lipid levels in 1577 youths aged 3 to 18 years in 1980. The subjects were randomly selected from five areas of Finland. ApoE phenotyping was performed directly from plasma by isoelectric focusing and immunoblotting. The apoE allele frequencies in the population sample were epsilon 2 = 0.039, epsilon 3 = 0.767, and epsilon 4 = 0.194. There were no differences in the apoE phenotype distribution between East and West Finland or between sexes. The concentrations of serum total cholesterol, low density lipoprotein cholesterol, and apolipoprotein B increased with apoE phenotype in the order of E2/2, E3/2, E4/2, E3/3, E4/3, and E4/4. This increase was already seen in 3-year-old children; it was observed in both sexes, but was clearer in males than in females. The mean levels of high density lipoprotein (HDL) cholesterol, apolipoprotein A-I, triglyceride, Lp[a] lipoprotein, and the activity of lecithin:cholesterol acyltransferase did not differ between the apoE phenotypes. The observed differences in serum cholesterol remained fairly stable during the 6-year follow-up from 1980 to 1986, while the mean serum cholesterol concentration in the whole study population decreased by 6.3%. This study confirms the reported higher frequency of the epsilon 4 allele in Finns as compared to most other populations; this may contribute to the high rates of CHD in Finland as compared to most other populations. The results do not, however, explain the higher rate of CHD in East Finland in comparison to the western part of the country.     

Clinical Characteristics of Refractory Myasthenia Gravis Patients

Background: A subset of myasthenia gravis (MG) patients is refractory to standard therapies. Identifying the characteristics of this population is essential as newer treatment strategies emerge that may be more effective in this group.Objective: The aim of our study is to describe the clinical features of refractory MG patients and compare them to those of non-refractory patients.Methods: A retrospective chart review was completed of 128 MG patients referred to a tertiary neuromuscular clinic from 2003 to 2011. Patients were classified as refractory or non-refractory based on predefined criteria, and clinical features were compared.Results: Nineteen out of 128 patients were classified as refractory (14.8 percent). Compared to the non-refractory patients, the refractory patients were more likely to be younger at onset, female, thymomatous, and MuSK-antibody positive.Conclusion: Refractory MG patients represent a small but distinct group for whom exploring newer therapeutic approaches and immunopathologic differences is warranted.     

Contributions of 18 additional DNA sequence variations in the gene encoding apolipoprotein E to explaining variation in quantitative measures of lipid metabolism

Apolipoprotein E (ApoE) is a major constituent of many lipoprotein particles. Previous genetic studies have focused on six genotypes defined by three alleles, denoted epsilon2, epsilon3, and epsilon4, encoded by two variable exonic sites that segregate in most populations. We have reported studies of the distribution of alleles of 20 biallelic variable sites in the gene encoding the ApoE molecule within and among samples, ascertained without regard to health, from each of three populations: African Americans from Jackson, Miss.; Europeans from North Karelia, Finland; and non-Hispanic European Americans from Rochester, Minn. Here we ask (1) how much variation in blood levels of ApoE (lnApoE), of total cholesterol (TC), of high-density lipoprotein cholesterol (HDL-C), and of triglyceride (lnTG) is statistically explained by variation among APOE genotypes defined by the epsilon2, epsilon3, and epsilon4 alleles; (2) how much additional variation in these traits is explained by genotypes defined by combining the two variable sites that define these three alleles with one or more additional variable sites; and (3) what are the locations and relative allele frequencies of the sites that define multisite genotypes that significantly improve the statistical explanation of variation beyond that provided by the genotypes defined by the epsilon2, epsilon3, and epsilon4 alleles, separately for each of the six gender-population strata. This study establishes that the use of only genotypes defined by the epsilon2, epsilon3, and epsilon4 alleles gives an incomplete picture of the contribution that the variation in the APOE gene makes to the statistical explanation of interindividual variation in blood measurements of lipid metabolism. The addition of variable sites to the genotype definition significantly improved the ability to explain variation in lnApoE and in TC and resulted in the explanation of variation in HDL-C and in lnTG. The combination of additional sites that explained the greatest amount of trait variation was different for different traits and varied among the six gender-population strata. The role that noncoding variable sites play in the explanation of pleiotropic effects on different measures of lipid metabolism reveals that both regulatory and structural functional variation in the APOE gene influences measures of lipid metabolism. This study demonstrates that resequencing of the complete gene in a sample of >/=20 individuals and an evaluation of all combinations of the identified variable sites, separately for each population and interacting environmental context, may be necessary to fully characterize the impact that a gene has on variation in related traits of a metabolic system.     

Isoform-Specific Effects of Apolipoprotein E on Markers of Inflammation and Toxicity in Brain Glia and Neuronal Cells In Vitro

Mutations to the cholesterol transport protein apolipoprotein E (ApoE) have been identified as a major risk factor for the development of sporadic or late-onset Alzheimer’s disease (AD), with the e4 allele representing an increased risk and the rare e2 allele having a reduced risk compared to the primary e3 form. The reasons behind the change in risk are not entirely understood, though ApoE4 has been connected to inflammation and toxicity in both the brain and the periphery. The goal of this study was to better understand how the ApoE isoforms (ApoE2/3/4) confer differential AD-related risk by assessing cell-specific ApoE-related neuroinflammatory and neurotoxic effects. We compared the effects of ApoE isoforms in vitro on human astrocytes, a human immortalized microglia cell line (HMC3), and the human neuroblastoma cell line SH-SY5Y. Cells were treated for 24 h with or without recombinant ApoE2, ApoE3, or ApoE4 (20 nM) and inflammation and toxicity markers assessed. Our results indicated the expression of inflammatory cytokines IL-1β, TNFα, and IL-6 in human astrocytes was increased in response to all ApoE isoforms, with ApoE4 evoking the highest level of cytokine expression. In response to ApoE2 or ApoE3, microglial cells showed reduced levels of microglial activation markers TREM2 and Clec7a, while ApoE4 induced increased levels of both markers. ApoE2 promoted neuron survival through increased BDNF release from astrocytes. In addition, ApoE2 promoted, while ApoE4 reduced, neuronal viability. Overall, these results suggest that ApoE4 acts on cells in the brain to promote inflammation and neuronal injury and that the deleterious effects of ApoE4 on these cells may, in part, contribute to its role as a risk factor for AD.     

Theophylline-Induced Seizures: Clinical and Pathophysiologic Aspects

The clinical features and management of theophylline-induced seizures are not well appreciated in spite of their unique aspects. These seizures tend to occur in neurologically intact patients and leave no or only minor neurologic sequelae if controlled early. They begin with focal motor seizures with or without secondary generalization and are followed by stupor or coma. They are responsive only to adjustment of theophylline dosage. Should the motor phenomenon persist, it takes the form of epilepsia partialis continua. Extensive workup for a structural brain lesion may be unrewarding. The electroencephalogram typically shows periodic lateralized epileptiform discharges, which may provide a diagnostic clue.     

Apolipoprotein E and apolipoprotein CI polymorphisms in the Czech population: almost complete linkage disequilibrium of the less frequent alleles of both polymorphisms

Apolipoproteins E and CI are the predominant components of triglyceride-rich lipoproteins. The genes are located in one gene cluster and both are polymorphic. Three allelic (epsilon2, epsilon3 and epsilon4) polymorphisms of the APOE gene influence plasma cholesterol levels. The distribution of these alleles differ between ethnic groups. PCR genotyping was used to determine the APOE and APOCI allele incidence in a representative group of 653 probands (302 men and 351 women) of Czech origin. The observed relative frequencies for the epsilon2, epsilon3 and epsilon4 alleles were 7.1 %, 82.0 % and 10.9 %, respectively, and are similar to other middle European populations. APO epsilon4 carriers have the highest and APO epsilon2 carriers the lowest levels of plasma total cholesterol (p<0.0001) and LDL cholesterol (p<0.0001). The frequency of the insertion (I) allele (HpaI restriction site present) of the APOCI polymorphism was 18.5 %. APOCI I/I homozygotes have the highest level of triglycerides (p<0.003). An almost complete linkage disequilibrium of the insertion allele of APOCI with the APOE alleles epsilon2 and epsilon4 has been detected and suggests that the deletion in the APOCI gene probably follows the deriving of all three APOE alleles on the APO epsilon3 allele background.     

12周高强度间歇训练对不同基因型载脂蛋白E血脂异常人群的调脂作用

目的:观察12周高强度间歇训练(HIIT)对不同载脂蛋白E(ApoE)基因型血脂异常人群的血脂调节作用。方法:通过测试空腹血脂指标,筛选出88例血脂异常患者作为受试对象,采集受试对象口腔粘膜进行载脂蛋白E基因型检测,测定12周高强度间歇训练干预前后的血脂水平。结果:88例血脂异常者中共检测出5种基因型,其分布为ApoE3/3＞ApoE3/4 ＞ApoE2/3＞ApoE2/2＞ApoE2/4,等位基因ε3＞ε2=ε4。运动干预前,血脂异常人群中ε4等位基因组的总胆固醇水平显著高于ε2和ε3基因组(P＜0.01),低密度脂蛋白胆固醇水平显著高于ε2基因组(P＜0.05),其余指标在各组间无显著性差异(P＞0.05)。12周的高强度间歇训练显著降低ε3基因组血清总胆固醇、甘油三酯和低密度脂蛋白胆固醇水平,升高高密度脂蛋白胆固醇水平。ε4基因组在运动干预后血清总胆固醇和低密度脂蛋白胆固醇降低,甘油三酯和高密度脂蛋白胆固醇无显著性改变。ε2基因组在运动干预后血清脂质无明显改善。结论:血脂异常人群载脂蛋白E基因多态性影响运动的调脂效果,12周高强度间歇训练可以作为ε3和ε4等位基因携带者调节血脂的运动干预方式。     

The role of epsilon 2/epsilon 3/epsilon 4 polymorphism of the apolipoprotein E gene in the development of dislipoproteinemia and its influence on the efficacy of the hypolipidemic therapy

Apolipoprotein E (apoE) isoforms have different affinity to lipoprotein (LP) receptors and lipids. In comparison with the "normal" apoE3 the apoE2 affinity to receptors is strictly decreased influencing its association with hypoholesterolemia and accumulation of LP of very-low density in the plasma. The apoE4 is characterized by the increased affinity to LP receptors and is associated with hyperholesterolemia (HCHL). In the homozygotes on allele E2 the gender, age, obesity, diabetes and some other factors have an influence on conversion of hypoholesterolemia to type Ill hyperlipidemia. The ApoE4 association with HCHL may be due to its impaired recycling in hepatocytes. The ApoE isoforms influence the hypolipidemic therapy efficacy: statins and physical training were more effective in epsilon2 allele carriers and probucol and low-fat diet had the maximal effect in epsilon4 allele carriers.     

Unique lipoproteins secreted by primary astrocytes from wild type, apoE (-/-), and human apoE transgenic mice.

Composition of central nervous system lipoproteins affects the metabolism of lipoprotein constituents within the brain. The epsilon4 allele of apolipoprotein E (apoE) is a risk factor for Alzheimer's disease via an unknown mechanism(s). As glia are the primary central nervous system cell type that synthesize apoE, we characterized lipoproteins secreted by astrocytes from wild type (WT), apoE (-/-), and apoE transgenic mice expressing human apoE3 or apoE4 in a mouse apoE (-/-) background. Nondenaturing size exclusion chromatography demonstrates that WT, apoE3, and apoE4 astrocytes secrete particles the size of plasma high density lipoprotein (HDL) composed of phospholipid, free cholesterol, and protein, primarily apoE and apoJ. However, the lipid:apoE ratio of particles containing human apoE is significantly lower than WT. ApoE localizes across HDL-like particle sizes. ApoJ localizes to the smallest HDL-like particles. ApoE (-/-) astrocytes secrete little phospholipid or free cholesterol despite comparable apoJ expression, suggesting that apoE is required for normal secretion of astrocyte lipoproteins. Further, particles were not detected in apoE (-/-) samples by electron microscopy. Nondenaturing immunoprecipitation experiments indicate that apoE and apoJ reside predominantly on distinct particles. These studies suggest that apoE expression influences the unique structure of astrocyte lipoproteins, a process further modified by apoE species.