Identifying differential regulatory control of APOE ɛ4 on African versus European haplotypes as potential therapeutic targets.

ABSTRACT: We previously demonstrated that in Alzheimer's disease (AD) patients, European apolipoprotein E (APOE) ε4 carriers express significantly more APOE ε4 in their brains than African AD carriers. We examined single nucleotide polymorphisms near APOE with significant frequency differences between African and European/Japanese APOE ε4 haplotypes that could contribute to this difference in expression through regulation. Two enhancer massively parallel reporter assay (MPRA) approaches were performed, supplemented with single fragment reporter assays. We used Capture C analyses to support interactions with the APOE promoter. Introns within TOMM40 showed increased enhancer activity in the European/Japanese versus African haplotypes in astrocytes and microglia. This region overlaps with APOE promoter

SUBMITTER: Nuytemans K 

PROVIDER: S-EPMC9250552 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature