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APOE mRNA and protein expression in postmortem brain are modulated by an extended haplotype structure. | LitMetric

APOE mRNA and protein expression in postmortem brain are modulated by an extended haplotype structure.

Am J Med Genet B Neuropsychiatr Genet

Geriatric Research, Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, Washington.

Published: March 2010

AI Article Synopsis

Article Abstract

Currently the epsilon4 allele of the apolipoprotein E gene (APOE) is the strongest genetic risk factor for late onset Alzheimer's disease (AD). However, inheritance of the APOE epsilon4 allele is not necessary or sufficient for the development of AD. Genetic evidence suggests that multiple loci in a 70 kb region surrounding APOE are associated with AD risk. Even though these loci could represent surrogate markers in linkage disequilibrium with APOE epsilon4 allele, they could also contribute biological effects independent of the APOE epsilon4 allele. Our previous study identified multiple SNPs upstream from APOE that are associated with cerebrospinal fluid apoE levels, suggesting that a haplotype structure proximal to APOE can influence apoE expression. In this study, we examined apoE expression in human post-mortem brain (PMB), and constructed chromosome-phase-separated haplotypes of the APOE proximal region to evaluate their effect on PMB apoE expression. ApoE protein expression was found to differ among AD brain regions and to differ between AD and control hippocampus. In addition, an extended APOE proximal haplotype structure, spanning from the TOMM40 gene to the APOE promoter, may modulate apoE expression in a brain region-specific manner and may influence AD disease status. In conclusion, this haplotype-phenotype analysis of apoE expression in PMB suggests that either; (1) the cis-regulation of APOE expression levels extends far upstream of the APOE promoter or (2) an APOE epsilon4 allele independent mechanism involving the TOMM40 gene plays a role in the risk of AD.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2829359PMC
http://dx.doi.org/10.1002/ajmg.b.30993DOI Listing

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