Allelic expression of APOE in human brain: Effects of epsilon status and promoter haplotypes
Abstract
The epsilon4 haplotype of APOE is the only undisputed genetic risk factor for late-onset Alzheimer's disease (LOAD). It has been proposed that at least two other polymorphisms in the promoter of the APOE gene (-219G>T and -491A>T) might also contribute to disease susceptibility, and modulate the impact of structural changes in the ApoE protein, by altering its expression. In order to assess the extent of cis-acting influences on APOE expression in human brain, highly quantitative measures of allele discrimination were applied to cortical RNA from individuals heterozygous for the epsilon alleles. A small, but significant, increase in the expression of epsilon4 allele was observed relative to that of the epsilon3 and epsilon2 alleles (P T promoter polymorphism revealed significantly lower relative expression of haplotypes containing the -219T allele (P=0.02). Our data indicate that, in human brain, most of the cis-acting variance in APOE expression is accounted for by the epsilon4 haplotype, but there are additional, small, cis-acting influences associated with promoter genotype.
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A number of studies investigating apoE expression and protein levels in the brain parenchyma as a function of APOE genotype have yielded controversial results.
“A number of studies investigating apoE expression and protein levels in the brain parenchyma as a function of APOE genotype have yielded controversial results (Beffert et al., 1999b; Bertrand et al., 1995; Bray et al., 2004; Growdon et al., 1999; Harr et al., 1996; Lambert et al., 1997; Pirttila et al., 1996).”
From The role of apolipoprotein E in Alzheimer's disease (2009) · cites this paper as Bray et al., 2004
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The role of apolipoprotein E in Alzheimer's disease
Kim, J., Basak, J. M., & Holtzman, D. M. (2009) · Neuron · doi:10.1016/j.neuron.2009.06.026 · Cited by 1,661 · see citing works
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- Authors
- Bray, N. J., Jehu, L., Moskvina, V., Buxbaum, J. D., Dracheva, S., Haroutunian, V., Williams, J., Buckland, P. R., Owen, M. J., & O'Donovan, M. C.
- Affiliations
- Cardiff University (GB)
- Corresponding author
- Bray, Nicholas J.
- ORCID
- Venue
- Human Molecular Genetics
- Publisher
- Oxford University Press (OUP)
- Published
- 2004-09-22
- Volume
- 13
- Issue
- 22
- Pages
- 2885-2892
- ISSN
- 0964-6906 (ISSN-L)
- 1460-2083
- OpenAlex
- W2107680694
- Cited by
- 45
- References
- 3
- Citations by year
- 2023: 2 · 2022: 2 · 2021: 4 · 2020: 1 · 2018: 1 · 2016: 2 · 2015: 2 · 2014: 2 · 2013: 1 · 2012: 3
- FWCI
- 1.95
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Human Molecular Genetics (publishedVersion)
- PubMed (publishedVersion)
- ORCA Online Research @Cardiff (Cardiff University) (submittedVersion)
- Research Portal (King's College London) (submittedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- Karolinska Institutet
- Medical Research Council
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- apolipoprotein E, allelic expression, promoter polymorphism, cis-acting regulation, Alzheimer's disease, allele discrimination, haplotype effects
- MeSH terms
- Alleles, Alzheimer Disease, Apolipoproteins E, Brain, Genotype, Haplotypes, Humans, Polymorphism, Genetic, Promoter Regions, Genetic, Genetic Predisposition to Disease, Apolipoprotein E4
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