apoE In Patients Research Articles

Abstract 14972: Association Between CEC Measured by Immobilized Liposome-Bound Gel Beads Method and the Size of Lipid-Rich Coronary Artery Plaque

Introduction/Background: High-density lipoprotein (HDL) exerts cholesterol efflux capacity (CEC), and it ameliorates cardiovascular disease (CVD). CEC had been expected as a surrogate biomarker in addition to HDL cholesterol (HDL-C), which has been found not always to reflect the CVD risk. However, the procedures of the conventional CEC assays were too complex to be introduced into clinical practice because of cell-based assay. Given this situation, we invented novel cell-free CEC assay named immobilized liposome-bound gel beads (ILG) method. ILG method utilizes liposomes which contain fluorescence labeled cholesterol instead of lipid loaded foam cells, and has advantage of simplicity of procedure and accuracy. Reserch Question/Hypothesis: Does ILG method show some associations between CEC and HDL subclass, and also reflect the condition of coronary artery plaque? Goals/Aim: We aim to demonstrate CEC by ILG method has clinical significance for assessment of the CVD risk. Methods/Approach: Patients who underwent diagnostic catheterization or percutaneous coronary intervention were enrolled, and 61 patients were examined through CEC analysis by ILG method and assessment of coronary artery plaque by optical coherence tomography (OCT) imaging. Large lipid-rich plaque was defined as a lipid plaque with a lipid arc ≥180°and lipid length ≥5 mm. Serum HDL subclass was analyzed by enzymatic assay (Denka). We defined the ratio apolipoprotein E(apoE)-containing HDL-C to HDL-C as %apoE, and we also calculated the value of HDL 3 -C/HDL 2 -C, and classified HDL 3 - or HDL 2 -rich group. Results/Data: HDL-C was positively associated with %apoE, and CEC of apoE-rich patients was higher than that of apoE-poor patients. This correlation was maintained after classified based on size of HDL. CEC and %apoE in patients with large lipid-rich plaque were significantly lower than in those in without. In contrast, there was no significant difference in HDL-C and LDL-C. Conclusion: In present study, ILG method showed that apoE has some influence on CEC, and CEC was inversely correlated with size of lipid-rich plaque. These results implied that ILG method, suitable CEC assay for clinical site, might be useful to assess the CVD risk.

Diagnosis of Familial Dysbetalipoproteinemia Based on the Lipid Abnormalities Driven by APOE2/E2 Genotype.

Familial dysbetalipoproteinemia (FDBL) is a monogenic disease due to variants in APOE with a highly variable phenotype. Current diagnostic lipid-based methods have important limitations. The objective is twofold: to define characteristics of dysbetalipoproteinemia (DBL) based on the analysis of APOE in patients from a lipid unit and in a sample from the general population, and to propose a screening algorithm for FDBL. Lipids and APOE genotype from consecutive unrelated subjects from Miguel Servet University Hospital (MSUH) (n 3603), subjects from the general population participants of the Aragon Workers Health Study (AWHS) (n 4981), and selected subjects from external lipid units (Ext) (n 390) were used to define DBL criteria and to train and validate a screening tool. Thirty-five subjects from MSUH, 21 subjects from AWHS, and 31 subjects from Ext were APOE2/2 homozygous. The combination of non high-density lipoprotein cholesterol (non-HDLc)/apoB 1.7 plus triglycerides/apoB 1.35, in mg/dL (non-HDLc [mmol/L]/apolipoprotein B (apoB) [g/L] 4.4 and triglycerides [mmol/L]/apoB [g/L] 3.5), provided the best diagnostic performance for the identification of subjects with hyperlipidemia and APOE2/2 genotype (sensitivity 100 in the 3 cohorts, and specificity 92.8 [MSUH], 80.9 [AWHS], and 77.6 [Ext]). This improves the performance of previous algorithms. Similar sensitivity and specificity were observed in APOE2/2 subjects receiving lipid-lowering drugs. The combination of non-HDLc/apoB and triglycerides/apoB ratios is a valuable tool to diagnose DBL in patients with hyperlipidemia with or without lipid-lowering drugs. FDBL diagnosis requires DBL and the presence of a compatible APOE genotype. Most adult APOE2/2 subjects express DBL, making FDBL as common as familial hypercholesterolemia in the population.

Relationship of APOE, age, amyloid and clinical phenotype in Alzheimer disease

AbstractBackgroundThe apolipoprotein ε4 (APOE4) allele is the most common and well established risk factor for typical late‐onset amnestic Alzheimer’s dementia. Less is known about the role of APOE in patients with atypical clinical presentations of AD, with studies often disagreeing on APOE4 frequencies in these cohorts. We aimed to assess relationships between APOE genotype and age, amyloid‐beta (Aβ) deposition and clinical phenotype in Alzheimer’s disease.Method138 atypical AD patients (57 posterior cortical atrophy and 81 logopenic aphasia) were recruited by the Neurodegenerative Research Group at Mayo Clinic, and underwent APOE testing and Pittsburgh Compound B PET. 318 typical AD patients with APOE genotype and known onset age were identified from ADNI (121 had Aβ‐PET). Aβ‐PET was quantified using the centiloid scale. Logistic regression was used to estimate the proportion of APOE4 carriers by onset age and clinical group. Linear regression was used to estimate mean Aβ centiloid by age, APOE4 status, and clinical group in patients who were Aβ‐positive (centiloid≥19).ResultThe overall frequency of APOE4 carriers was lower in atypical AD (52%) compared to typical AD (66%), particularly for ε4ε4 homozygotes (9% vs 20%). APOE4 frequency increased with age in atypical AD, but showed a bell‐shaped curve in typical AD where highest frequencies were observed between 65‐70 years (Figure). Typical AD showed higher APOE4 frequencies than atypical AD only between the ages of 57 and 69 years. Aβ centiloid was higher in atypical AD compared to typical AD by approximately 16 centiloid units, but did not differ according to APOE4 status (Figure). Aβ centiloid stayed relatively flat with increasing age for both carriers and non‐carriers in atypical AD, but declines with increasing age in typical AD. Relationships between APOE4 and age, as well as centiloid, did not differ between the two atypical AD phenotypes.ConclusionAPOE4 frequency differs between atypical and typical AD but is highly dependent upon age, with higher APOE4 frequency in typical AD only observed between 57 and 69 years. The findings highlight the importance of age and clinical phenotype in understanding the effects of APOE genotype in Alzheimer’s disease.

Varied Relationship of Lipid and Lipoprotein Profiles to Liver Fat Content in Phenotypes of Metabolic Associated Fatty Liver Disease.

BackgroundProgressive overloads of intrahepatic triglycerides are related to metabolic dysregulation of multiple lipid and lipoprotein profiles, but whether similar dose effects are found in each subtype of metabolic associated fatty liver disease (MAFLD) remains unclear. We aimed to characterize the lipid profiles associated with liver fat content (LFC) in MAFLD patients who were overweight, lean/normal weight, or had diabetes.MethodsWe conducted a cross-sectional study enrolling 1,182 consecutive participants (144 non-MAFLD and 1,038 MAFLD) who underwent MRI proton density fat fraction measurement (MRI-PDFF) from 2011 to 2020. Lipid and apolipoprotein profiles, free fatty acid (FFA), liver and metabolism parameters, and anthropometric measurements were also assessed.ResultsMAFLD patients with type 2 diabetes or overweight/obesity had a higher proportion of abnormal lipid and lipoprotein profiles than those who were lean/normal weight. The degree of LFC had a positive correlation with total cholesterol, triglyceride, ApoB, and ApoE in patients with overweight/obesity and type 2 diabetes. In those with overweight/obesity, there were dose–response relationships between moderate-to-severe steatosis and total cholesterol, triglyceride, HDL-c, LDL-c, ApoB, ApoE, and Lp(a). A similar trend was observed for triglyceride in those with type 2 diabetes and for HDL-c in patients who were lean/normal weight (all p for trend <0.05). The combined model of relative lipid-related markers performed well in the prediction of moderate-to-severe steatosis (AUC: 0.762 for overweight/obesity; 0.742 for lean/normal weight).ConclusionLFC was associated with lipid profiles, including triglyceride, LDL-c, ApoB, ApoE, and FFA. These relationships were varied by the phenotype of MAFLD according to its diagnostic flow.

&lt;p&gt;Identification of Apolipoprotein E as a Potential Diagnostic Biomarker of Nasopharyngeal Carcinoma&lt;/p&gt;

PurposeApo-E, a secreted protein, is closely related to the migration and invasion of tumor cells. In this study, we aimed to analyze the expression of Apo-E in nasopharyngeal carcinoma (NPC) patients and cell lines, as well as its effects on NPC cell behavior.Patients and MethodsOur study included 35 patients with NPC from Zhongnan Hospital. Expression levels of Apo-E in patients with NPC were examined by quantitative reverse transcription-polymerase chain reaction, Western blot, and immunohistochemical (IHC) staining. Receiver operating characteristic (ROC) curves were analyzed using the SPSS 22 software to estimate the sensitivity and specificity of the Apo-E protein in diagnosing NPC. Additionally, the level of Apo-E in NPC cell lines (NP69, 6–10B, and 5–8F) was investigated by Western blotting and IHC.ResultsLevels of Apo-E were higher in NPC patients than in controls. Moreover, ROC analysis revealed that increased Apo-E in the serum of NPC patients may act as a potential biomarker for NPC diagnosis (Area under the curve 0.917). Furthermore, similar results were also identified in NPC cancer cell lines. RNA interference technology was used to overexpress the endogenous Apo-E in the NPC cell line 6–10B. Wound healing and transwell assays indicated that the overexpression of Apo-E increased the number of cell colonies and migration ability, respectively.ConclusionIn this study, we found that Apo-E was elevated in NPC patients and may act as a potential biomarker for NPC diagnosis. In addition, Apo-E was upregulated in NPC cell lines and promoted cell growth, migration, and invasion.

Prevalence of candidate single nucleotide polymorphisms on p53, IL-11, IL-10, VEGF and APOE in patients with repeated implantation failure (RIF) and pregnancy loss (RPL)

Recurrent pregnancy loss (RPL; defined as the loss of three or more consecutive pregnancies) and recurrent implantation failure (RIF; when implantation is not achieved after at least three cycles of IVF) are two of the major challenges that reproductive medicine faces. Some polymorphisms have been identified as possible causes of an increased risk of these diseases. This paper studies the prevalence of the polymorphisms in p53, VEGF, IL-10, IL-11 and APOE in RIF and RPL patients that determines the risk for these pathologies. A total of 255 patients were selected (89 RPL patients, 77 RIF patients and 89 controls) and genotyped for p53-R72P; IL-11-1082-AG; VEGF-1154-AG; IL-10; APOE-R112C; APOE-R158C. Statistically significant differences were found in the prevalence of the E4 isoform (R122-R158) of the APOE gene in RPL patients (p < 0.05), and in RIF patients, the R72P polymorphism of the p53 gene and the 1154-AG of the VEGF gene showed different distribution (p < 0.05). Regarding the p53 and IL-11 studied polymorphisms, PP of p53 gene and GG of IL-11 are more prevalent in RPL patients without reaching statistical significance. In conclusion, our results suggest patients carrying variants in p53 and VEGF would be at risk of RIF, and those carrying variants in APOE gene would suffer RPL.

Genes polymorphism of BIN1 and ApoE in patients with amnestic mild cognitive impairment from Enshi Tujia area

Objective: To investigate the polymorphism of BIN1 and ApoE genes in amnestic mild cognitive impairment (aMCI) patients in Tujia minority area of Enshi, Hubei. Methods: A total of 107 patients with aMCI (aMCI group) and 150 healthy people (healthy control group) during the same period were included between December 2016 and October 2017 in Affiliated Minda Hospital of Hubei University for Nationalities, who were all the Tujia nationality. Three single nucleotide polymorphic site of BIN1 gene rs744373, rs7561528, rs6733839, and two single nucleotide polymorphic site of ApoE gene rs429358, rs7412, and Genotyping and sub-genotyping of ApoE genes were tested using ligase detection reaction technique(LDR), and gene polymorphisms of BIN1 and ApoE were analyzed with Logistic regression analysis. Results: The basic information was not statistically significan different between healthy control group and aMCI group (P>0.05); there were no statistically significant in genotype distribution among the 3 SNPs of BIN1 gene(rs744373, rs7561528, rs6733839) and between the 2 SNPs of ApoE gene(rs429358, rs7412) and its allelic profile (P>0.05), which conformed to Hardy-Weinberg balance; BIN1 gene rs744373 polymorphic site allele C was the risk factor of aMCI (OR 2.33, 95% CI 1.09-4.98, P=0.029), especially BIN1 gene rs744373 polymorphic site recessive model CC/CT+ TT increased the risk of aMCI disease (OR 2.29, 95% CI 1.15-4.59, P=0.019). The difference in genotype distribution of ApoE sub-genotype ε2/2, ε2/3, ε2/4, ε3/3, ε3/4, ε4/4 and allele ε2, ε3, ε4 genes between two groups were significantly different (P<0.05), Carrying ApoEε2 may be a protective factor for aMCI (OR 0.46, 95% CI 0.22-0.96, P=0.039) and carrying ApoE ε4 may be a risk factor for aMCI (OR 2.13, 95% CI 1.18-3.83, P=0.012). Conclusions: The incidence of aMCI in Tujia region of Enshi may be related to the rs744373 polymorphic site of BIN1 gene, ApoEε2 is the protective factor and ApoEε4 is the risk factor for aMCI in Tujia region of Enshi, but it still needs to be further verified by a large sample population.

Apolipoprotein E Gene Variants on the Risk of End Stage Renal Disease

ObjectiveEnd-stage renal disease (ESRD) is a severe health concern over the world. Associations between apolipoprotein E (apoE) gene polymorphisms and the risk of ESRD remained inconclusive. This study aimed to investigate the association between apoE gene polymorphisms and ESRD susceptibility.MethodsDatabases including PubMed, Embase, Web of Science and the Cochrane Library were searched to find relevant studies. Meta-analysis method was used synthesize the eligible studies. ResultsSixteen pertinent case-control studies which included 3510 cases and 13924 controls were analyzed. A significant association was found between ε2 allele and the ESRD risk (odds ratio (OR) = 1.30, 95% confidence interval (CI) 1.15–1.46, P < 0.0001; I 2 = 18%, P for heterogeneity = 0.24). The ε2ε3, ε2ε4, ε3ε3, ε3ε4, ε4ε4, ε3 and ε4 were not associated with the susceptibility of ESRD. In the subgroup analysis by ethnicity, there was a statistically significant association between ε2ε3 or ε2 allele and ESRD risk in East Asians (OR = 1.66, 95% CI 1.31–2.10, P < 0.0001; OR = 1.62, 95% CI 1.31–2.01, P < 0.0001, respectively), but not in Caucasians. E2 carriers had higher plasma apoE (mean difference = 16.24 mg/L, 95% CI 7.76-24.73, P = 0.0002) than the (ε3 + ε4) carriers in patients with ESRD. The publication bias was not significant.ConclusionThe ε2 allele of apoE gene might increase the risk of ESRD. E2 carriers expressed higher level of plasma apoE in patients with ESRD. More well-designed studies are needed to confirm these associations in the future.

Development of an MRM assay panel with application to biobank samples from patients with myocardial infarction

As part of a Swedish national cardiological research initiative, the development of a quantitative MRM assay is reported for the quantification of eleven putative cardiovascular disease markers. Within the study, patient samples from the LUNDHEARTGENE biobank were processed and nanoLC-MS/MS analysis was performed together with a stable isotope dilution strategy for absolute quantification of the target proteins. Excellent linear regressions were achieved for 9 of the 11 peptides with LOQ ranged in the attomolar range. We have utilized the assay for the screening of plasma samples from patients with chest pain, and performed a comparative analysis of patients with ST-segment elevation myocardial infarction and chest pain due to other causes. The assay demonstrates high reproducibility and correlate with clinical findings. Strong correlations were found for several of the apolipoproteins and their respective lipid subfractions (LDL, HDL or triglycerides). APOC1, APOC2 and APOE were elevated in patients with STEMI. An MRM assay were developed for putative cardiovascular disease markers as target proteins, and applied to biobanking sample material. The comparative analysis of patients with ST-segment elevation myocardial infarction and chest pain due to other causes showed elevated levels of APOC1, APOC2 and APOE in patients with STEMI. These observations raise interesting novel hypotheses about the role of apolipoproteins C1, C2 and E in the pathophysiology of acute myocardial infarction, which merits further studies.

Association of Apolipoprotein E ε2 With White Matter Disease but Not With Microbleeds

Apolipoprotein E (apoE) alleles (epsilon2 and epsilon4) are associated with cerebral amyloid angiopathy, in which white matter disease and microbleeds are prominent features. The role of apoE in patients with microbleeds or white matter disease but no evidence of cerebral amyloid angiopathy has not been elucidated. We studied apoE alleles in relation to white matter disease and microbleeds in patients with transient ischemic attack or ischemic stroke. We obtained brain MRI scans and apoE genotypes in 334 transient ischemic attack or ischemic stroke patients. Microbleeds were scored on a gradient echo MRI and white matter disease was examined on fluid attenuated inversion recovery MRI using a semiquantitative rating scale. Patients with moderate to severe white matter disease more frequently carried apoE epsilon2 alleles (25.2% versus 11.3%, P=0.001), but not apoE epsilon4 (26.6% in apoE epsilon4 carriers versus 25.9%; P=0.98). Adjustment for traditional risk factors did not modify this relationship (odds ratio, 2.9; 95% confidence interval, 1.5 to 5.3). There was no association between the presence of microbleeds and the apoE epsilon4 or apoE epsilon2 alleles. ApoE alleles do not exert a major influence on the development of microbleeds, but apoE epsilon2 may be associated with development of moderate to severe white matter disease in transient ischemic attack and stroke patients.

Study on relationship between polymorphism of apolipoprotein E gene and syndromes of phlegm and blood stasis in patients with coronary heart disease

To explore the relationship between polymorphism of apolipoprotein E (ApoE) exon 4 gene and different syndromes in patients with coronary heart disease (CHD). Two hundred patients with CHD were divided into four groups according to syndrome differentiation, including syndrome of phlegm (PS), syndrome of blood stasis (BSS), syndrome of phlegm-blood stasis blocking (PBBS) and syndrome of non-phlegm and non-blood stasis (NPNBS). One hundred healthy volunteers were included in control group. Blood lipids were measured by routine examination. Total DNA of peripheral blood was extracted. ApoE genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. All data were analyzed by SAS software. (1)The occurrence rate of epsilon4 allele of ApoE in patients with CHD was 19.5%, significantly higher than 9.5% in the control group (P<0.05), and the E 3/4 genotype was especially more frequent (P<0.01). (2) The levels of total cholesterol (TC), total triglycerides (TG) and low-density lipoprotein cholesterol (LDL-C) in patients with epsilon4 were higher than those in patients without epsilon4 (P<0.01). (3) The frequencies of epsilon4 allele and E3/4 genotype in patients with PS were significantly higher than those in patients with BSS (P<0.05). ApoE epsilon4 allele, especially E3/4 genotype, is the risk factor of CHD. There is a relatively close relationship between patients with ApoE epsilon4 allele and PS. It may be one of the main susceptible genes in CHD patients with PS.

Overproduction of apoE in patients with type III hyperlipoproteinemia and in patients with other forms of hypertriglyceridemia

Overproduction of apoE in patients with type III hyperlipoproteinemia and in patients with other forms of hypertriglyceridemia

672 Longitudinal study of CSF amyloid proteins and apoE in patients with Alzheimer's disease

672 Longitudinal study of CSF amyloid proteins and apoE in patients with Alzheimer's disease