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Association study of Notch 4 polymorphisms with Alzheimer's disease
- Source :
- Journal of Neurology, Neurosurgery & Psychiatry. 75:377-381
- Publication Year :
- 2004
- Publisher :
- BMJ, 2004.
-
Abstract
- Background: The NOTCH4 gene is located at 6p21.3, a site shown in several studies to have significant linkage with Alzheimer’s disease. Objective: To investigate the potential impact of two polymorphisms within this gene on the risk of developing Alzheimer’s disease. Methods: Genotyping of promoter and 5′-UTR polymorphisms was done in Scottish, English, and French populations. The potential functionality of the 5′-UTR polymorphism was assessed by testing its impact on Aβ load in Alzheimer brains and also by undertaking electrophoretic mobility shift assays and transfection experiments. Results: No association of the Notch4 polymorphisms alone with the disease was observed in any of the populations. However, an interaction of the 5′-UTR C/T polymorphism with the e4 allele of the APOE gene was detected in United Kingdom populations but not in the French. No relation between the 5′-UTR polymorphism and Aβ loads was detected overall or in the presence or absence of the e4 allele. No DNA protein specific binding was found with proteins from neuroblastoma, glioma, or astrocytoma cells, and no allele dependent transcriptional activity was detected. Conclusions: No association between two NOTCH4 polymorphisms alone and Alzheimer’s disease was observed in the three populations, but there was evidence of an increased risk associated with the 5′-UTR CC genotype in e4 bearers in the United Kingdom. As no functionality for this polymorphism could be determined, it is likely that the interaction is spurious or results from a linkage disequilibrium of this 5′-UTR polymorphism with another marker elsewhere in the 6p21.3 locus.
- Subjects :
- Male
Paper
Apolipoprotein E
Linkage disequilibrium
Genotype
Receptors, Cell Surface
Locus (genetics)
macromolecular substances
Biology
Major Histocompatibility Complex
Alzheimer Disease
Risk Factors
Proto-Oncogene Proteins
medicine
Humans
Genetic Predisposition to Disease
Age of Onset
Allele
Receptor, Notch4
Gene
Genotyping
Aged
Genetics
Polymorphism, Genetic
Receptors, Notch
Middle Aged
medicine.disease
Psychiatry and Mental health
Cross-Sectional Studies
Genetics, Population
England
Scotland
Immunology
Chromosomes, Human, Pair 6
Female
Surgery
France
Neurology (clinical)
Alzheimer's disease
5' Untranslated Regions
Subjects
Details
- ISSN :
- 00223050
- Volume :
- 75
- Database :
- OpenAIRE
- Journal :
- Journal of Neurology, Neurosurgery & Psychiatry
- Accession number :
- edsair.doi.dedup.....33ce6af3d47702ea544806390050beb0