ArticleHuman molecular genetics2013
Epigenetic signature and enhancer activity of the human APOE gene.
Article in Human molecular genetics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
42 citing papers in PubMed, 1 synthesis or guideline pooled it, 69 citations in OpenAlex.
- Blood DNA methylation as a potential biomarker of dementia: A systematic review.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2018Pooled it
- Haplotype-resolved DNA methylation at theNPJ dementia · 2026Article
- Interplay Between 3D Chromatin Architecture and Gene Regulation at theInternational journal of molecular sciences · 2025Article
- Review
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- The Impact of Apolipoprotein E (Biology · 2023Review
- The APOE-TOMM40 Humanized Mouse Model: Characterization of Age, Sex, and PolyT Variant Effects on Gene Expression.Journal of Alzheimer's disease : JAD · 2023Article
- Genetic Determinants of Plasma Low-Density Lipoprotein Cholesterol Levels: Monogenicity, Polygenicity, and "Missing" Heritability.Biomedicines · 2021Review
- Identification of epigenome-wide DNA methylation differences between carriers of APOE ε4 and APOE ε2 alleles.Genome medicine · 2021Article
- Recent Evidence in Epigenomics and Proteomics Biomarkers for Early and Minimally Invasive Diagnosis of Alzheimer's and Parkinson's Diseases.Current neuropharmacology · 2021Review
- Differential DNA methylation in familial hypercholesterolemia.EBioMedicine · 2020Article
- Identification of Key Genes in Gastric Cancer by Bioinformatics Analysis.BioMed research international · 2020Article
- DNA methylation in APOE: The relationship with Alzheimer's and with cardiovascular health.Alzheimer's & dementia (New York, N. Y.) · 2020Article
- Redefining transcriptional regulation of the APOE gene and its association with Alzheimer's disease.PloS one · 2020Article
- Overall and sex-specific associations between methylation of the ABCG1 and APOE genes and ischemic stroke or other atherosclerosis-related traits in a sibling study of Chinese population.Clinical epigenetics · 2019Article
- Differential Methylation inInternational journal of molecular sciences · 2019Article
- Could Alzheimer's Disease Originate in the Periphery and If So How So?Molecular neurobiology · 2019Review
- Evaluation of α-synuclein and apolipoprotein E as potential biomarkers in cerebrospinal fluid to monitor pharmacotherapeutic efficacy in dopamine dictated disease states of Parkinson's disease and schizophrenia.Neuropsychiatric disease and treatment · 2019Article
- The impact of APOE genotype on survival: Results of 38,537 participants from six population-based cohorts (E2-CHARGE).PloS one · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
Abstract
The human apolipoprotein E (APOE) gene plays an important role in lipid metabolism. It has three common genetic variants, alleles ε2/ε3/ε4, which translate into three protein isoforms of apoE2, E3 and E4. These isoforms can differentially influence total serum cholesterol levels; therefore, APOE has been linked with cardiovascular disease. Additionally, its ε4 allele is strongly associated with the risk of Alzheimer's disease (AD), whereas the ε2 allele appears to have a modest protective effect for AD. Despite decades of research having illuminated multiple functional differences among the three apoE isoforms, the precise mechanisms through which different APOE alleles modify diseases risk remain incompletely understood. In this study, we examined the genomic structure of APOE in search for properties that may contribute novel biological consequences to the risk of disease. We identify one such element in the ε2/ε3/ε4 allele-carrying 3'-exon of APOE. We show that this exon is imbedded in a well-defined CpG island (CGI) that is highly methylated in the human postmortem brain. We demonstrate that this APOE CGI exhibits transcriptional enhancer/silencer activity. We provide evidence that this APOE CGI differentially modulates expression of genes at the APOE locus in a cell type-, DNA methylation- and ε2/ε3/ε4 allele-specific manner. These findings implicate a novel functional role for a 3'-exon CGI and support a modified mechanism of action for APOE in disease risk, involving not only the protein isoforms but also an epigenetically regulated transcriptional program at the APOE locus driven by the APOE CGI.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.