Skip Navigation



Human Molecular Genetics Advance Access published online on July 5, 2007
Human Molecular Genetics, doi:10.1093/hmg/ddm171
This Article
Right arrow Advance Access manuscript (PDF) Freely available
Right arrow All Versions of this Article:
16/18/2199    most recent
ddm171v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Belbin, O.
Right arrow Articles by Morgan, K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Belbin, O.
Right arrow Articles by Morgan, K.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2007. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Regulatory region single nucleotide polymorphisms of the apolipoprotein E gene and the rate of cognitive decline in Alzheimer's disease

Olivia Belbin1, Janette L. Dunn2, Yan Ling1, Linda Morgan1, Sally Chappell1, Helen Beaumont3, Donald Warden3, David Smith3, Noor Kalsheker1 and Kevin Morgan1,*

1 Division of Clinical Chemistry, Institute of Genetics, Queen's Medical Centre, University of Nottingham, NG7 2UH, UK 2 School of Physics and Astronomy, University of Nottingham, University Park, Nottingham NG7 2RD, UK 3 OPTIMA, Oxford Centre for Gene Function, Department of Physiology, Anatomy & Genetics, Oxford, OX1 3PT, UK

* Corresponding author Kevin Morgan, Fax: +44 (0)115 9709167, Tel: +44 (0)115 8230724 Email: Kevin.morgan{at}nottingham.ac.uk

Received May 11, 2007; Revised June 28, 2007; Accepted June 28, 2007

The aim of this study was to investigate if single nucleotide polymorphisms (SNPs) in the regulatory regions of the apolipoprotein E (APOE) gene modify the well-established {varepsilon}4-associated risk for Alzheimer's disease (AD). Sequencing of the APOE gene regulatory regions, revealed four previously reported promoter SNPs and one novel SNP in the previously described macrophage enhancer (ME.1). In addition we also studied the two classic allelic mis-sense SNPs that define {varepsilon}2/ {varepsilon}3/ {varepsilon}4 status in a case-control association study. Analysis of pair-wise linkage disequilibrium (LD) of the five regulatory region SNPs with classic APOE SNPs revealed a previously unreported 7kb LD block covering the entire APOE gene, part of the promoter and 3' enhancer region. We report here that in a case-control association study (N=719) of the seven SNPs, the genotype at codon 112 captures all the information required to assess disease risk. To explore correlations with quantitative traits, 169 patients were studied in whom rates of cognitive decline were available. In addition to the {varepsilon}4 allele, two regulatory region SNPs were associated with the rate of cognitive decline in AD patients. This study highlights the effect of APOE gene variation on risk of AD and rate of cognitive decline and demonstrates that a single SNP, that confers {varepsilon}4 status, captures all of the risk of developing AD but two SNPs in the regulatory region may affect the rate of cognitive decline in AD patients.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.