Publication
Title
Genetic variability in the regulatory region of presenilin 1 associated with risk for Alzheimer's disease and variable expression
Author
Abstract
Mutations in the presenilin 1 (PSEN1) gene have been implicated in 18-50% of autosomal dominant cases with early-onset Alzheimer's disease (EOAD). Also, PSEN1 has been suggested as a potential risk gene in late-onset AD cases. We recently showed genetic association in a population-based study of EOAD, pointing to the 5′ regulatory region of PSEN1. In this study we systematically screened 3.5 kb of the PSEN1 upstream region and found four novel polymorphisms. Genetic analysis confirmed association of two polymorphisms with increased risk for EOAD. In addition, we detected two different mutations in EOAD cases at -280 and -2818 relative to the transcription initiation site in exon 1A of PSEN1. Analysis of the mutant and wild-type -280 variants using luciferase reporter gene expression in transiently transfected neuroblastoma cells showed a 30% decrease in transcriptional activity for the mutant -280G PSEN1 promoter variant compared with the wild-type variant -280C. Our data suggest that the increased risk for EOAD associated with PSEN1 may result from genetic variations in the regulatory region leading to altered expression levels of the PSEN1 protein.
Language
English
Source (journal)
Human molecular genetics. - Oxford
Publication
Oxford : 2000
ISSN
0964-6906
Volume/pages
9:3(2000), p. 325-331
ISI
000085380800001
Full text (Publishers DOI)
Full text (publishers version - intranet only)
UAntwerpen
Faculty/Department
Research group
Publication type
Affiliation
Publications with a UAntwerp address
External links
Web of Science
Record
Identification
Creation 08.10.2008
Last edited 22.04.2017
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