title: Risk for Alzheimer's disease correlates with transcriptional activity of the APOE gene.
abstract: While the straightepsilon4 allele of apolipoprotein E ( APOE, gene; ApoE, protein) is widely accepted as a major genetic risk factor for the late onset form of Alzheimer's disease (AD), recent evidence points to variations in ApoE levels as another important factor. We have previously reported that a common variant in the regulatory region of APOE (-491A) is associated with risk for late onset AD. In this report we analyze the association of another APOE promoter polymorphism (-427T/C) with AD in two case-control clinical samples and demonstrate a correlation between APOE promoter transcriptional activity and risk for AD. The association studies show that the allelic variant (-427C) and the haplotype [-491A-427C] of the APOE promoter are associated with increased risk for AD. Study of the transcriptional activity of the common haplotypes defined by combination of the -491 and -427 alleles indicated that the risk for late onset AD positively correlates with transcriptional activity of the APOE gene, suggesting that increases in the local expression of ApoE could be responsible for the association of APOE promoter polymorphism with AD.
authors.affiliation: Departamento de Biología Molecular and Centro de Biología Molecular Severo Ochoa (CSIC-UAM), 28049 Madrid, Spain.
authors.forename: M J
authors.initials: MJ
authors.lastname: Artiga
authors.forename: M J
authors.initials: MJ
authors.lastname: Bullido
authors.forename: A
authors.initials: A
authors.lastname: Frank
authors.forename: I
authors.initials: I
authors.lastname: Sastre
authors.forename: M
authors.initials: M
authors.lastname: Recuero
authors.forename: M A
authors.initials: MA
authors.lastname: García
authors.forename: C L
authors.initials: CL
authors.lastname: Lendon
authors.forename: S W
authors.initials: SW
authors.lastname: Han
authors.forename: J C
authors.initials: JC
authors.lastname: Morris
authors.forename: J
authors.initials: J
authors.lastname: Vázquez
authors.forename: A
authors.initials: A
authors.lastname: Goate
authors.forename: F
authors.initials: F
authors.lastname: Valdivieso
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000544:Alzheimer Disease / Q000235:genetics*; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics*; D005786:Gene Expression Regulation; D005787:Gene Frequency; D005796:Genes / Q000235:genetics*; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics; D012307:Risk Factors; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
chemical_list: D053327:Apolipoprotein E4; D001057:Apolipoproteins E