Title
**APP** and **BACE1** miRNA genetic variability has no major role in risk for Alzheimer disease **APP** and **BACE1** miRNA genetic variability has no major role in risk for Alzheimer disease
Author
Faculty/Department
Faculty of Pharmaceutical, Biomedical and Veterinary Sciences . Biomedical Sciences
Publication type
article
Publication
New York, N.Y. ,
Subject
Human medicine
Source (journal)
Human mutation. - New York, N.Y.
Volume/pages
30(2009) :8 , p. 1207-1213
ISSN
1059-7794
ISI
000268742500009
Carrier
E
Target language
English (eng)
Full text (Publishers DOI)
Affiliation
University of Antwerp
Abstract
Expression levels of the amyloid precursor protein (APP) and -site amyloid (A) cleaving enzyme 1 (BACE1) have been implicated in Alzheimer disease (AD) progression. In a well-characterized Belgian group of 358 AD patients and 462 controls, we examined whether genetic variability in microRNA (miRNA) binding sites of APP and BACE1 or in associated miRNAs influenced risk for AD. Direct sequencing identified six variants in the 3 untranslated region (UTR) of APP and 29 variants in the 3 UTR of BACE1, of which few variants were restricted to patients: in APP; 4 variants in 6 patients (2%) and in BACE1; 7 variants in 11 patients (3.5%). Further genetic screening of the miR-29 cluster encoding the miR-29a/b-1 genes showed 10 variants in close proximity of this cluster. Association studies using all common variants detected in the 3 UTR of BACE1 and the miR-29 gene cluster did not identify an association with AD risk. However, we did observe statistical interaction between rs535860 (BACE1 3 UTR) and rs34772568 (near miR29a; odds ratio [OR]interaction, 0.4; 95% confidence interval [CI], 0.17-0.96; P=0.033). While the exact role of the patient-specific miRNA variants within the 3 UTR region of APP and BACE1 demands further analyses, this study does not support a major contribution of miRNA genetic variability to AD pathogenesis.
E-info
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000268742500009&DestLinkType=RelatedRecords&DestApp=ALL_WOS&UsrCustomerID=ef845e08c439e550330acc77c7d2d848
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000268742500009&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=ef845e08c439e550330acc77c7d2d848
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000268742500009&DestLinkType=CitingArticles&DestApp=ALL_WOS&UsrCustomerID=ef845e08c439e550330acc77c7d2d848
Handle