Expression of APOE gene allele-specific brain transcripts of European and African ancestries

Abstract

The APOE gene is identified as a major risk factor for late onset Alzheimer's disease and has three alleles, µ2, µ3 and µ4, related to two non-synonymous substitutions. The presence of the µ4 allele confers an increased risk for the disease in a dose dependent manner (odds ratio 12.9 for homozygous individuals and between 3.2 and 4.2 for heterozygous individuals). The most prevalent form of Alzheimer's disease has a multifactorial etiology, where several genetic and environmental factors influence its pathology. Factors such as age and sex are relevant in determining the risk for APOE, recent studies point out that the ancestry around the APOE gene is also relevant to the risk for the disease. Individuals of African-American ancestry have a reduced risk of developing the disease compared to European and Asian whites. These regions may act in a cis-regulatory manner in modulating gene expression. The Brazilian population results from miscegenation between indigenous, African and European populations, offering an opportunity to study the effects of different ancestry on the risk of Alzheimer's disease. Thus, this project aims to quantitatively characterize the role of different local ancestry in the different APOE genotypes by associating them with the expression of this gene through molecular marker genotyping and RT-qPCR techniques. It is expected that the expression is differentially increased when European ancestry is shown to be present, compared to non-European ancestry, and may explain, in part, the difference in risks observed in populations of different ancestries. (AU)