Abstract
Genetic association has been reported between a di-allelic polymorphism in intron 8 of presenilin-1 (PSEN1) and Alzheimer's disease (AD) in some studies but not in others. In a population-based series of 102 patients with early onset AD and 118 community controls we examined whether polymorphisms in linkage disequilibrium with intron 8 of PSEN1 may explain the association. In addition to the intron 8 polymorphism (P = 0.05), a promoter polymorphism (P = 0.03) and the simple tandem repeat (STR) polymorphism D14S1028 located upstream of PSEN1 (P = 0.04) were found to be marginally significantly associated to AD. When excluding PSEN1 mutation cases (n = 6), the intron 8 association was explained by linkage disequilibrium to the dominant PSEN1 mutations. In the non-mutation cases, the weak associations between the polymorphisms in the regulatory region remained. Our study suggests that a polymorphism/mutation in the promoter or regulatory region of PSEN1 rather than the polymorphism in intron 8 of PSEN1 is associated with early onset AD.
Similar content being viewed by others
Article PDF
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Duijn, C., Cruts, M., Theuns, J. et al. Genetic association of the presenilin-1 regulatory region with early-onset Alzheimer's disease in a population-based sample. Eur J Hum Genet 7, 801–806 (1999). https://doi.org/10.1038/sj.ejhg.5200373
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.ejhg.5200373
Keywords
This article is cited by
-
Alzheimer’s Disease and Frontotemporal Dementia: The Current State of Genetics and Genetic Testing Since the Advent of Next-Generation Sequencing
Molecular Diagnosis & Therapy (2018)
-
ProphNet: A generic prioritization method through propagation of information
BMC Bioinformatics (2014)
-
Normal Japanese individuals harbor polymorphisms in the p14 ARF /INK4 locus promoters and/or other gene introns. — Variation in nucleotide sequences in each individual
Genes & Genomics (2011)
-
Regulatory region variability in the human presenilin-2 (PSEN2) gene: potential contribution to the gene activity and risk for AD
Molecular Psychiatry (2002)
-
Lack of replication of association findings in complex disease: an analysis of 15 polymorphisms in prior candidate genes for sporadic Alzheimer's disease
European Journal of Human Genetics (2001)