Back to Search
Start Over
APP and BACE1 miRNA genetic variability has no major role in risk for Alzheimer disease.
- Source :
-
Human mutation [Hum Mutat] 2009 Aug; Vol. 30 (8), pp. 1207-13. - Publication Year :
- 2009
-
Abstract
- Expression levels of the amyloid precursor protein (APP) and beta-site amyloid (Abeta) 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 ( approximately 2%) and in BACE1; 7 variants in 11 patients ( approximately 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.
- Subjects :
- 3' Untranslated Regions
Aged
Base Sequence
Female
Humans
Male
Middle Aged
Alzheimer Disease genetics
Amyloid Precursor Protein Secretases genetics
Amyloid beta-Protein Precursor genetics
Aspartic Acid Endopeptidases genetics
Genetic Predisposition to Disease
Genetic Variation
MicroRNAs genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1098-1004
- Volume :
- 30
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Human mutation
- Publication Type :
- Academic Journal
- Accession number :
- 19462468
- Full Text :
- https://doi.org/10.1002/humu.21027