APP and BACE1 miRNA genetic variability has no major role in risk for Alzheimer disease†
Karolien Bettens
Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerp, Belgium
Laboratory of Neurogenetics, Institute Born-Bunge, Antwerp, Belgium
University of Antwerp, Antwerp, Belgium
Search for more papers by this authorNathalie Brouwers
Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerp, Belgium
Laboratory of Neurogenetics, Institute Born-Bunge, Antwerp, Belgium
University of Antwerp, Antwerp, Belgium
Search for more papers by this authorSebastiaan Engelborghs
Laboratory of Neurochemistry and Behavior, Institute Born-Bunge, Antwerp, Belgium
University of Antwerp, Antwerp, Belgium
Memory Clinic and Division of Neurology, ZNA Middelheim, Antwerp, Belgium
Search for more papers by this authorHelen Van Miegroet
Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerp, Belgium
Laboratory of Neurogenetics, Institute Born-Bunge, Antwerp, Belgium
University of Antwerp, Antwerp, Belgium
Search for more papers by this authorPeter P. De Deyn
Laboratory of Neurochemistry and Behavior, Institute Born-Bunge, Antwerp, Belgium
University of Antwerp, Antwerp, Belgium
Memory Clinic and Division of Neurology, ZNA Middelheim, Antwerp, Belgium
Search for more papers by this authorJessie Theuns
Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerp, Belgium
Laboratory of Neurogenetics, Institute Born-Bunge, Antwerp, Belgium
University of Antwerp, Antwerp, Belgium
Search for more papers by this authorKristel Sleegers
Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerp, Belgium
Laboratory of Neurogenetics, Institute Born-Bunge, Antwerp, Belgium
University of Antwerp, Antwerp, Belgium
Search for more papers by this authorCorresponding Author
Christine Van Broeckhoven
Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerp, Belgium
Laboratory of Neurogenetics, Institute Born-Bunge, Antwerp, Belgium
University of Antwerp, Antwerp, Belgium
Department of Molecular Genetics, Neurodegenerative Brain Diseases Group, VIB and University of Antwerp–CDE, Parking P4, Building V, Room 0.10, Universiteitsplein 1, B-2610 Antwerp, BelgiumSearch for more papers by this authorKarolien Bettens
Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerp, Belgium
Laboratory of Neurogenetics, Institute Born-Bunge, Antwerp, Belgium
University of Antwerp, Antwerp, Belgium
Search for more papers by this authorNathalie Brouwers
Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerp, Belgium
Laboratory of Neurogenetics, Institute Born-Bunge, Antwerp, Belgium
University of Antwerp, Antwerp, Belgium
Search for more papers by this authorSebastiaan Engelborghs
Laboratory of Neurochemistry and Behavior, Institute Born-Bunge, Antwerp, Belgium
University of Antwerp, Antwerp, Belgium
Memory Clinic and Division of Neurology, ZNA Middelheim, Antwerp, Belgium
Search for more papers by this authorHelen Van Miegroet
Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerp, Belgium
Laboratory of Neurogenetics, Institute Born-Bunge, Antwerp, Belgium
University of Antwerp, Antwerp, Belgium
Search for more papers by this authorPeter P. De Deyn
Laboratory of Neurochemistry and Behavior, Institute Born-Bunge, Antwerp, Belgium
University of Antwerp, Antwerp, Belgium
Memory Clinic and Division of Neurology, ZNA Middelheim, Antwerp, Belgium
Search for more papers by this authorJessie Theuns
Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerp, Belgium
Laboratory of Neurogenetics, Institute Born-Bunge, Antwerp, Belgium
University of Antwerp, Antwerp, Belgium
Search for more papers by this authorKristel Sleegers
Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerp, Belgium
Laboratory of Neurogenetics, Institute Born-Bunge, Antwerp, Belgium
University of Antwerp, Antwerp, Belgium
Search for more papers by this authorCorresponding Author
Christine Van Broeckhoven
Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerp, Belgium
Laboratory of Neurogenetics, Institute Born-Bunge, Antwerp, Belgium
University of Antwerp, Antwerp, Belgium
Department of Molecular Genetics, Neurodegenerative Brain Diseases Group, VIB and University of Antwerp–CDE, Parking P4, Building V, Room 0.10, Universiteitsplein 1, B-2610 Antwerp, BelgiumSearch for more papers by this authorCommunicated by Garry R. Cutting
Abstract
Expression levels of the amyloid precursor protein (APP) and β-site amyloid (Aβ) 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. Hum Mutat 30:1–7, 2009. © 2009 Wiley-Liss, Inc.
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