ArticleAmerican journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics2010
Functional characterization of three single-nucleotide polymorphisms present in the human APOE promoter sequence: Differential effects in neuronal cells and on DNA-protein interactions.
Article in American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.
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Who cites it
32 citing papers in PubMed, 1 synthesis or guideline pooled it, 43 citations in OpenAlex.
- The landscape of GWAS validation; systematic review identifying 309 validated non-coding variants across 130 human diseases.BMC medical genomics · 2022Pooled it
- Effects of Molecular Hydrogen Assessed by an Animal Model and a Randomized Clinical Study on Mild Cognitive Impairment.Current Alzheimer research · 2018Trial
- Apolipoprotein E2 Expression Alters Endosomal Pathways in a Mouse Model With Increased Brain Exosome Levels During Aging.Traffic (Copenhagen, Denmark) · 2024Article
- Exploring the role of apolipoprotein E gene promoter polymorphisms in susceptibility to normal-tension glaucoma in a Korean population.Scientific reports · 2024Article
- Effects of microRNA-298 on APP and BACE1 translation differ according to cell type and 3'-UTR variation.Scientific reports · 2022Article
- The Effects of rs405509 onFrontiers in neuroscience · 2021Article
- Iron-responsive-like elements and neurodegenerative ferroptosis.Learning & memory (Cold Spring Harbor, N.Y.) · 2020Review
- Blood biomarkers for memory: toward early detection of risk for Alzheimer disease, pharmacogenomics, and repurposed drugs.Molecular psychiatry · 2020Article
- Role of Apolipoprotein E, Cathepsin D, and Brain-Derived Neurotrophic Factor in Parkinson's Disease: A Study from Eastern India.Neuromolecular medicine · 2019Article
- The role of APOE in transgenic mouse models of AD.Neuroscience letters · 2019Review
- The Transcriptional Regulatory Properties of Amyloid Beta 1-42 may Include Regulation of Genes Related to Neurodegeneration.Neuromolecular medicine · 2018Article
- Disrupted Brain Structural Connectivity: Pathological Interactions Between Genetic APOE ε4 Status and Developed MCI Condition.Molecular neurobiology · 2017Article
- Discovery of Novel Human Gene Regulatory Modules from Gene Co-expression and Promoter Motif Analysis.Scientific reports · 2017Article
- Association between polymorphisms in the promoter region of the apolipoprotein E (APOE) gene and Alzheimer's disease: A meta-analysis.EXCLI journal · 2017Article
- Is there a significant interaction effect between apolipoprotein E rs405509 T/T and ε4 genotypes on cognitive impairment and gray matter volume?European journal of neurology · 2016Article
- Daidzein Augments Cholesterol Homeostasis via ApoE to Promote Functional Recovery in Chronic Stroke.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2015Article
- Significance of NF-κB as a pivotal therapeutic target in the neurodegenerative pathologies of Alzheimer's disease and multiple sclerosis.Expert opinion on therapeutic targets · 2015Review
- The effects of an APOE promoter polymorphism on human cortical morphology during nondemented aging.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2015Article
- Gata5 deficiency causes airway constrictor hyperresponsiveness in mice.American journal of respiratory cell and molecular biology · 2014Article
- Cognitive changes preceding clinical symptom onset of mild cognitive impairment and relationship to ApoE genotype.Current Alzheimer research · 2014Article
Corrections and comments
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Authors and funding
7 authors at 5 institutions in 3 countries.
Funding
Abstract
Variations in levels of apolipoprotein E (ApoE) have been tied to the risk and progression of Alzheimer's disease (AD). Our group has previously compared and contrasted the promoters of the mouse and human ApoE gene (APOE) promoter sequences and found notable similarities and significant differences that suggest the importance of the APOE promoter's role in the human disease. We examine here three specific single-nucleotide polymorphisms within the human APOE promoter region, specifically at -491 (A/T), -427 (T/C), and at -219 (G/T) upstream from the +1 transcription start site. The -219 and -491 polymorphic variations have significant association with instance of AD, and -491AA has significant risk even when stratified for the APOEepsilon4 allele. We also show significant effects on reporter gene expression in neuronal cell cultures, and, notably, these effects are modified by species origin of the cells. The -491 and -219 polymorphisms may have an interactive effect in addition to any independent activity. DNA-protein interactions differ between each polymorphic state. We propose SP1 and GATA as candidates for regulatory control of the -491 and -219 polymorphic sites. This work's significance lies in drawing connection among APOE promoter polymorphisms' associations with AD to functional promoter activity differences and specific changes in DNA-protein interactions in cell culture-based assays. Taken together, these results suggest that APOE expression levels are a risk factor for AD irrespective of APOEepsilon4 allele status.
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