ApoE4 increases glycogen synthase kinase 3β expression and Tau phosphorylation in U87 cells / 南方医科大学学报

<p><b>OBJECTIVE</b>To explore the relations among apolipoprotein E4, Tau protein and glycogen synthase kinase 3β (GSK-3β).</p><p><b>METHODS</b>U87 cells were transfected with pIRES-EGFP (control) or the recombinant plasmids ApoE4/pIRES-EGFP or ApoE3/pIRES-EGFP, and the expression levels of p-Tau/Tau and GSK-3β in the cells were examined with Western blotting. To further confirm the effect of ApoE on GSK-3β and p-Tau expressions, a short interfering RNA (siRNA) targeting ApoE (ApoE-siRNA) was transfected into U87 cells via Lipofectamine 2000 and the protein expressions were examined 24 h later.</p><p><b>RESULTS</b>Compared with those in the control group, the expressions levels of both GSK-3β and p-Tau/Tau increased significantly in the cells transfected with ApoE4 and ApoE3 plasmids (P<0.01), and the ApoE4 plasmid produced a more potent effect than the ApoE3 plasmid on the protein expressions (P<0.01). ApoE knockdown resulted in significantly reduced expressions of GSK-3β (P<0.001) and p-Tau (P<0.01) in the cells.</p><p><b>CONCLUSION</b>ApoE4 can enhance Tau phosphorylation though upregulating GSK-3β, which sheds light on a new role of ApoE4 in Alzheimer's disease.</p>

Gestational hyperlipidemia and acute pancreatitis with underlying partial lipoprotein lipase deficiency and apolipoprotein E3/E2 genotype

We report the case of a patient who experienced extreme recurrent gestational hyperlipidemia. She was diagnosed with partial lipoprotein lipase (LPL) deficiency but without an associated LPL gene mutation in the presence of the apolipoprotein E3/2 genotype. This is the first reported case of extreme gestational hyperlipidemia with a partial LPL deficiency in the absence of an LPL gene mutation and the apolipoprotein E 3/2 genotype. She was managed with strict dietary control and medicated with omega-3 acid ethyl esters. A patient with extreme hyperlipidemia that is limited to the gestational period should be considered partially LPL-deficient. Extreme instances of hyperlipidemia increase the risk of acute pancreatitis, and the effect of parturition on declining plasma lipid levels can be immediate and dramatic. Therefore, decisions regarding the timing and route of delivery with extreme gestational hyperlipidemia are critical and should be made carefully.

Discrepancy in Genotyping of Apolipoprotein E between Allele-Specific PCR and Fluorescence Resonance Energy Transfer or Sequencing / 대한진단검사의학회지

The human apolipoprotein E (APOE) gene contains several single-nucleotide polymorphisms (SNPs) that are distributed across the gene. The genotype of the APOE gene has important implications as a risk factor for various diseases. We observed 2 cases in which the results of allele-specific PCR (AS-PCR) of the APOE gene were not consistent with those of fluorescence resonance energy transfer (FRET) or sequencing analysis. In these cases, genotyping by AS-PCR showed that patients were epsilon2 homozygotes, while sequencing analysis and FRET showed that they were epsilon2/epsilon3 heterozygotes. Herein, we describe the causes of the errors in genotyping and describe the significance of these errors.

Association of Apolipoprotein E Gene Polymorphism With Cognitive Function of the Elderly Residents in a Rural Community

BACKGROUND: It is not clear whether polymorphism of the apolipoprotein E (ApoE) gene influences the cognition of community residents. The aim of this study was to establish the association between ApoE gene polymorphism and cognitive function in an elderly rural community in Korea. METHODS: A total of 388 subjects aged 65 and over were recruited. Demographic characteristics, past history of illness, and scores on the Korean version of the Mini Mental State Examination (K-MMSE), the Geriatric Depression Scale . Short Form (GDS-S), and the Korean version of Instrumental Activities of Daily Living (K-IADL) were evaluated. The lipid profile and ApoE genotype were sampled from 377 of the participants. RESULTS: Of the entire cohort, 75% had less than 6 years of education, and 30% were illiterate. The frequencies of the ApoE epsilon2, ApoE epsilon3, and ApoE epsilon4 alleles were 48 (6.6%), 372 (86.9%), and 49 (6.5%), respectively. The K-MMSE score was much lower in those with two ApoE epsilon3 alleles than in those with only one ( p=0.046). However, the numbers of ApoE epsilon2 alleles (p=0.976) and ApoE epsilon4 alleles (p=0.934) carried by the individual were not associated with K-MMSE score. Both K-IADL (p<0.001) and GDS-S (p<0.001) scores were significantly correlated with K-MMSE score. Grouping of the participants into three groups according to K-MMSE score (i.e., 0-17 , 18-24, and 25-30) also revealed that this score was correlated with K-IADL score (p<0001), GDS-S score (p<0.001), and the ApoE epsilon3 allele (p=0.035). CONCLUSIONS: These results suggest that the ApoE epsilon3 allele has a negative influence on cognitive function (K-MMSE) in this rural community. Surprisingly, we were unable to detect any relationship between the ApoE epsilon4 allele and cognitive function. There was a positive correlation between K-MMSE, K-IADL, and GDS-S scores.

Apolipoprotein E Phenotypes and the Relationship Among Lipid Levels, Nutrient Intakes, Lifestyles and Risk Factors Between Subjects with and without Hyperlipidemic Risk

This study was performed to investigate Apolipoprotein E phenotypes and the relationship among lipid levels, nutrient intakes, lifestyles and risk factors between subjects with and without hyperlipidemic risk. The data were collected from 675 industrial male workers who had completed annual medical examination. Compared to the normal group, the hyperlipidemic risk group in Apo E3 and E4 had significantly higher BMI (p < 0.05) and showed significantly higher body fat (%), waist circumference and WHR in all types of Apo E (p < 0.05). In addition, the hyperlipidemic risk group had significantly higher total cholesterol, LDL-cholesterol, triglyceride and AI than the normal group in all types of Apo E (p < 0.05). Intakes of protein, calcium, phosphorus, iron, vitamin A, vitamin B1, vitamin B2, vitamin C and niacin in Apo E3 were significantly lower in the hyperlipidemic risk group than in the normal group (p < 0.05). In the logistic regression analysis, after adjustment for other factors, Apo E2 + E4, waist and WHR were the significant risk factors associated with hyperlipidemia, but protein intakes were associated with significantly lower risks of hyperlipidemia (p < 0.05). In conclusion, genetic factor (Apo E2 or Apo E4), anthropometric index and nutrient intake seem to influence hyperlidemic risk. Further studies and efforts will be needed to evaluate the independent relationships among hyperlipidemic risk factors.

Blood Lipid Levels, Nutrient Intakes and Health-Related Lifestyles of Industrial Male Workers According to Apolipoprotein E Polymorphisms / 대한지역사회영양학회지

The purpose of this study was to investigate the association among nutrient intakes and health-related lifestyles with cardiovascular disease risk assessed by blood lipid profile according to Apolipoprotein E genotypes. Middle-aged industrial male workers who had completed their annual medical examination were recruited and data of 675 subjects who finished the nutrient survey were used in the analysis. Anthropometric parameters, dietary assessment (FFQ), health-related lifestyles and blood profiles were used for statistical analyses. Apo E genotype groups were classified into the following three genotypes: Apo E2 group (including E2/E2, E2/E3, E2/E4), Apo E3 group (including E3/E3), Apo E4 group (including E3/E4, E4/E4). The frequency of Apo E2, E3, and E4 allele were 13.3%, 75.0% and 11.7% respectively. There were no significant differences in the anthropometric parameters depending on different Apo E genotypes. Also, no significant differences in the nutrient intakes were found according to the genotype groups. The nutrient intakes of all subjects were similar to or higher than the level of KDRIs (Dietary Reference Intakes For Koreans) except for intakes of calcium (67.44% of KDRIs), vitamin A (73.83% of KDRIs) and vitamin B2 (78.02% of KDRIs). Also, there were no significant differences of health-related lifestyles according to Apo E genotype groups. As for the lipid profiles, Apo E4 group had significantly higher total and LDL-cholesterol concentrations than the Apo E2 group (p < 0.05). We confirmed that plasma total and LDL-cholesterol concentrations were greatly influenced by Apo E genotypes. However, nutrient intakes and health-related lifestyles were not associated with Apo E genotypes.

Association of apolipoprotein E polymorphisms with serum lipid profiles in obese adolescent / 소아과

PURPOSE: Apolipoprotein E (Apo E) plays a major role in lipoprotein metabolism and lipid transport. Many investigators have described that Apo E polymorphisms is one of the most important genetic determinants for cardiovascular disease. The purpose of this study was to evaluate the association between Apo E polymorphisms and serum lipid profiles in obese adolescent. METHODS: We measured the serum concentrations of glucose, apolipoprotein (Apo) A1, Apo B, total cholesterol (TC), triglyceride (TG), HDL and LDL-cholesterol after overnight fasting in obese adolescent. Apo E polymorphisms were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: 86 obese adolescents participated in this study. The body mass index (BMI) of participants were excess of 95 percentile by age and sex. Male to female ratio was 1.7 and mean age of study group was 16.2+/-1.8 years. Mean BMI was 27.4+/-2.5 kg/m2. The frequency of epsilon2, epsilon3 and epsilon4 allele were 8.1%, 87.2% and 4.7% respectively. Study populations were classified into the following three genotypes 1) Apo E2 group (n=13, 15.1%) carrying either the epsilon2/epsilon2 or epsilon2/epsilon3 2) Apo E3 group (n=65, 75.6%) carrying the most frequent epsilon3/epsilon3 3) Apo E4 group (n=8, 9.3%) carrying either the epsilon3/epsilon4 or epsilon4/epsilon4. No differences were found among Apo E genotypes concerning age, sex, weight, height and BMI. Apo B and LDL-cholesterol concentrations were significantly higher in the Apo E4 group (P<0.05). No association were found between Apo E genotypes and glucose, Apo A1, TC, TG and HDL. CONCLUSIONS: We confirmed that serum concentrations Apo B and LDL-cholesterol were influenced by Apo E genotypes. Apo E polymorphisms seems to influence some alteration of lipid metabolism associated with obesity in adolescent.

Evaluation of neuroprotective effects of long-term low dose hormone replacement therapy on postmenopausal women brain hippocampus using magnetic resonance scanner / 中国医学科学杂志(英文版)

<p><b>OBJECTIVE</b>To investigate the effects of long-term low dose hormone replacement therapy (HRT) on postmenopausal women in hormone level, cognition score, hippocampus volume, and magnetic resonance spectroscopy (MRS) parameters.</p><p><b>METHODS</b>A total of 182 postmenopausal women aged 50-87 years were chosen at Peking Union Medical College Hospital and assigned to HRT group and control group. The volunteers of HRT group had taken low dose hormone [estradiol (E2) 0.5-1.0 mg and progesterone 0.5-2.0 mg, once a day] for 4-33 years. The concentrations of E2, progesterone, and testosterone were measured using enzyme-linked immunosorbent assay (ELISA). The gene types of apolipoprotein E (ApoE) were measured by polymerase chain reaction, and the subjects with susceptible genes (ApoE epsilon3/epsilon4) of Alzheimer's disease (AD) were screened. Their hippocampus volumes and MRS parameters were obtained through magnetic resonance imaging (MRI), and results in two groups were analyzed by statistical method.</p><p><b>RESULTS</b>Compared with control group, the concentrations of E2 at each age stage in HRT group were significantly higher (P < 0.05) except the 80-89 years old subgroup; yet, there were no statistical differences in the concentrations of progesterone and testosterone between the two groups. There was no obvious difference in ApoE subtypes distribution between the two groups. The results of hippocampus MRI for the subjects with susceptible genes ApoE epsilon3/epsilon4 (HRT group 14 cases, control group 11 cases) showed that the ratio of bilateral hippocampus volume to whole brain volume in HRT group (0.406 +/- 0.028) was significantly higher than control group (0.369 +/- 0.031, P < 0.05). The results of 1H MRS for the subjects with susceptible genes ApoE epsilon3/epsilon4 (HRT group 12 cases, control group 11 cases) showed that the N-acetylaspartate/total creatine at the area of hippocampus in HRT group (1.54 +/- 0.08) were significantly higher than control group (1.45 +/- 0.13, P < 0.05).</p><p><b>CONCLUSIONS</b>For postmenopausal women, long-term low dose HRT can maintain the physiological concentration of E2 in plasma. Furthermore, the hippocampus MRI performed on those with ApoE epsilon3/epsilon4 genes shows that long-term low dose HRT can prevent hippocampus atrophy, which is beneficial to maintain the brain function and prevent AD.</p>

Plasma level and genetic variation of apolipoprotein E in patients with lipoprotein glomerulopathy / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Lipoprotein glomerulopathy (LPG) is a renal disease characterized by thrombus-like lipoproteins in the glomerular capillaries and its abnormal lipoprotein profiles with marked elevation of apolipoprotein E (apoE). In this study, 15 Chinese patients with LPG were involed in exploring the association of the genetic variation and its plasma level in the pathogenesis of LPG.</p><p><b>METHODS</b>A retrospective analysis of the clinical and pathological features was made in 15 patients with LPG. Plasma concentrations of apoE were measured with radial immunodiffusion assay. Genetic variations of apoE gene were detected using polymerase chain reaction and restriction fragment length polymorphism. Glomerular deposition of apoA, apoB and apoE in these patients were detected by immunofluorescence staining using monoclonal antibodies.</p><p><b>RESULTS</b>Biochemical profiles of lipids and lipoproteins revealed markedly elevated levels of triglyceride, apoB and apoE, but approximately normal levels of total cholesterol, apoA1 and lipoprotein(a) [Lp(a)], which resembled familial hypertriglyceridemia. Genetic analysis demonstrated that the genotype distribution of apoE were 7 cases with epsilon3/epsilon4, 4 cases with epsilon3/epsilon3 and 2 cases with epsilon2/epsilon3. The other 2 cases (a mother and her son) showed a same distinct band. The band pattern of later 2 cases was quite similar to the apoE variant of Tokyo type. The calculated allele frequency of epsilon 4 was relatively high in cases with LPG in comparison with that in the normal controls. We further divided the 13 patients into three groups according to their genotypes of apoE. Patients with the genotype of apoE epsilon2/epsilon3 showed a lower level of plasma apoE as compared to those with apoE epsilon3/epsilon4 (P < 0.05). The serum level of high-density lipoprotein (HDL) was the lowest in patients with the genotype of apoE epsilon3/epsilon4. No difference was found among the patients with different apoE genotype in the other clinical and pathological characteristics.</p><p><b>CONCLUSIONS</b>The genotype of apoE epsilon3/epsilon4 is the predominant one in Chinese patients with LPG. Patients with this genotype tend to have a higher plasma level of apoE and more severe lipid dysmetabolism. No correlation was found between the genotype of apoE and the clinical features in patients with LPG.</p>

Apolipoprotein E and ACE genetic polymorphism and nephropathy in type 2 diabetic patients / 대한내과학회지

BACKGROUND: The aim of this study was to investigate the association between apo E and ACE genetic polymorphism and diabetic nephropathy. METHODS: One hundred eighteen patients with type 2 diabetes who had a duration of diabetes longer than 8 years were divided into the three apo E groups (E2, E3, E4) and three ACE groups (II, ID, DD). Plasma levels of lipids were measured. The frequency of diabetic nephropathy and clinical and biochemical characteristics were compared among the Apo E and ACE genotype groups. RESULTS: The frequency of overt nephropathy was significantly greater in apo E2 patients with diabetes (46.7%) than apo E3 (16.7%) or apo E4 patients (10.5%). Logistical regression analysis showed that odds ratio of apo E2 and apo E4 genotypes for the presence of overt nephropathy were 4.779 (p<0.01) and 0.643 (p=0.583), respectively. Plasma TG levels were significantly greater in apo E2 patients. This study did not show an association between ACE gene polymorphism and diabetic nephropathy, and no interaction between Apo E and ACE gene polymorphism. CONCLUSION: Apo E2 is a prognostic risk factor for diabetic nephropathy in Korean type 2 diabetes. TG may have an important role of diabetic nephropathy. There were not synergistic effect between Apo E and ACE gene polymorphism in diabetic nephropathy.

Study on apoE gene polymorphism and subclasses of serum high density lipoprotein in type IV hyperlipidemia / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>The aim of the study was to investigate apolipoprotein(apo) E polymorphism and its relationship with serum lipids and apolipoprotein, serum high density lipoprotein(HDL) subclasses in patients with type IV hyperlipidemia.</p><p><b>METHODS</b>apoE genotype was assayed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The subclasses of serum HDL in 103 patients with type IV hyperlipidemia and 146 normolipidemic subjects were determined by two-dimensional gel electrophoresis in conjunction with immunodetection method.</p><p><b>RESULTS</b>The apoE3/3 genotype frequency and allele epsilon 3 frequency were both the highest in the frequency distribution profiles of the type IV hyperlipidemia group and the control group. In type IV hyperlipidemia group, the genotype of apoE2 had higher serum HDL-C,apoE, HDL(2a) apoE/apoCIII ratio but lower TG/HDL-C,apoCIII, HDL(3c) levels when compared with the genotype of apoE(3) (P<0.05). In control group, the genotype of apoE(2) had higher serum TG, apoE levels and apoE/aopCIII ratio but lower HDL (3a) level when compared with the genotype of apoE(3) (P<0.05).</p><p><b>CONCLUSION</b>An association of allele epsilon 2 of apoE gene with the maturation of HDL in type IV hyperlipidemia was noted in the study.</p>

Relationship of APOE gene polymorphism with subclasses of serum high density lipoprotein in hyperlipidemia / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate apolipoprotein E(apoE) polymorphism and its relationship with serum lipids and apolipoprotein, serum high density lipoprotein (HDL) subclasses in patients with hyperlipidemia(HL).</p><p><b>METHODS</b>APOE genotype was assayed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The subclasses of serum HDL in 112 patients with hyperlipidemia and 73 healthy subjects were determined by two-dimensional gel electrophoresis in conjunction with immunodetection method.</p><p><b>RESULTS</b>APOE3/3 genotypes and allele epsilon3 frequency in HL group and control group were both the highest. In HL group, the genotype of APOE2 had higher serum APOE/CIII ratio and lower HDL3b levels, compared with the genotype of APOE3 (P<0.05). In control group, the genotype of apoE2 had higher serum triglycerides, APOE levels and APOE/CIII ratio, compared with the genotype of APOE3 and APOE4 (P<0.05).</p><p><b>CONCLUSION</b>Polymorphism of APOE gene may relate to the distribution of HDL particles.</p>

Analysis of the APOE Alleles in Mental Retardation without Chromosome Anomaly / 대한해부학회지

APOE (apolipoprotein E) has been as a risk factor for Alzheimer's disease. Studies demonstrated that there was no significant differences in APOE distribution compared with controls and there was also a report showing a lower frequency of APOE E4 allele in an elderly Down's syndrome population than in a control group. We examined the distribution of APOE alleles in people with mental retardation having normal chromosome constitute. We studied 55 mental retardation individuals without chromosome anomaly and compared the frequency of APOE allele with 89 control samples. The APOE genotype was determined by HhaI restriction enzyme analysis of DNA amplified by polymerase chain reaction. The frequencies of APOE alleles in mental retardation patients were 3.6% (epsilon2), 88.2% (epsilon3), and 8.2% (epsilon4). The frequencies in controls were 10.1% (epsilon2), 73.6% (epsilon3), and 16.3% (epsilon4). The frequencies of APOE epsilon2 and epsilon4 alleles in mental retardation patients were significant lower than that in controls (p<0.05), but the frequency of APOE epsilon3 allele was higher reversely (p<0.01). These results suggest that APOE alleles are associated with mental retardation although the biological role of APOE in pathogenesis of mental retardation is unknown.