@article{02d3b840f5da420eae6562f1509bc8f3,
title = "Risk for Alzheimer's disease correlates with transcriptional activity of the APOE gene",
abstract = "While the ε4 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.",
author = "Artiga, {M. J.} and Bullido, {M. J.} and A. Frank and I. Sastre and M. Recuero and Garc{\'i}a, {M. A.} and Lendon, {C. L.} and Han, {S. W.} and Morris, {J. C.} and J. V{\'a}zquez and A. Goate and F. Valdivieso",
note = "Funding Information: We thank P. Alonso of the Hospital Ram{\'o}n y Cajal of Madrid for her kind collaboration in sample collection, P. Barreiro-Tella and E. D{\'i}ez-Tejedor of the Hospital La Paz of Madrid for advice on clinical work and the faculty and staff of the Washington University Alzheimer{\textquoteright}s Disease Research Center for patient evaluation and sample collection. We thank J. Baty of the Washington University Division of Biostatistics for advice on statistical analysis. We thank F. Mayor for his continuous encouragement and help. We thank the patients and healthy individuals who participated in this research. This work was supported by Boehringer Ingelheim Espa{\~n}a, Fondo de Investiga-ci{\'o}n Sanitaria (grant no. 95-0022), NIH (AG05681 and AG03991), the Alzheimer{\textquoteright}s Association, the Nettie and Rebecca Brown Foundation and the Metropolitan Life Foundation. The institutional grant from the Fundaci{\'o}n Ram{\'o}n Areces to CBMSO is acknowledged. M.J.A. is the recipient of a fellowship from the Fondo de Investigaci{\'o}n Sanitaria. M.A.G. is the recipient of a fellowship from the Spanish Ministerio de Educaci{\'o}n y Ciencia.",
year = "1998",
month = nov,
doi = "10.1093/hmg/7.12.1887",
language = "English",
volume = "7",
pages = "1887--1892",
journal = "Human molecular genetics",
issn = "0964-6906",
number = "12",
}