Genetic association of the APP binding protein 2 gene (APBB2) with late onset Alzheimer disease

Li, Y., Hollingworth, P., Moore, P., Foy, C., Archer, N., Powell, J., Nowotny, P., Holmans, Peter Alan ORCID: https://orcid.org/0000-0003-0870-9412, O'Donovan, Michael Conlon ORCID: https://orcid.org/0000-0001-7073-2379, Tacey, K., Doil, L., van Luchene, R., Garcia, V., Rowland, V., Lau, K., Cantanese, J., Sninsky, J., Hardy, J., Thal, L., Morris, J. C., Goate, A., Lovestone, S., Owen, Michael John ORCID: https://orcid.org/0000-0003-4798-0862, Williams, Julie ORCID: https://orcid.org/0000-0002-4069-0259 and Grupe, A. 2005. Genetic association of the APP binding protein 2 gene (APBB2) with late onset Alzheimer disease. Human Mutation 25 (3) , pp. 270-277. 10.1002/humu.20138

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Abstract

Alzheimer disease (AD) is a complex neurodegenerative disorder predisposed by multiple genetic factors. Mutations in amyloid beta precursor protein (APP) are known to be associated with autosomal dominant, early onset familial AD and possibly also late onset AD (LOAD). A number of genes encoding proteins capable of binding to APP have been identified, but their contribution to AD pathobiology remains unclear. Conceivably, mutations in these genes may play a role in affecting AD susceptibility, which appears to be substantiated by some genetic studies. Here we report results of the first genetic association study with APBB2, an APP binding protein (also known as FE65L), and LOAD, in three independently collected case-control series totaling approximately 2,000 samples. Two SNPs were significantly associated with LOAD in two sample series and in meta-analyses of all three sample sets (for rs13133980: odds ratio [OR](hom)=1.36 [95% CI: 1.05-1.75], OR(het)=1.32 [95% CI: 1.04-1.67], minor allele frequency=43%, P=0.041; and for hCV1558625: OR(hom)=1.37 [95% CI: 1.06-1.77], OR(het)=1.02 [95% CI: 0.82-1.26], minor allele frequency=48%, P=0.026). One of these SNPs, located in a region conserved between the human and mouse genome, showed a significant interaction with age of disease onset. For this marker, the association with LOAD was most pronounced in subjects with disease onset before 75 years of age (OR(hom)=2.43 [95% CI: 1.61-3.67]; OR(het)=2.15 [95% CI: 1.46-3.17]; P=0.00006) in the combined sample set. Our data raise the possibility that genetic variations in APBB2 may affect LOAD susceptibility.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG) Neuroscience and Mental Health Research Institute (NMHRI)
Subjects:	R Medicine > R Medicine (General)
Publisher:	Wiley-Blackwell
ISSN:	1059-7794
Last Modified:	31 Oct 2022 10:04
URI:	https://orca.cardiff.ac.uk/id/eprint/83537

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