Interaction between theADAM12 andSH3MD1 genes may confer susceptibility to late-onset Alzheimer's disease

Harold, Denise, Jehu, Luke, Turic, Darko, Hollingworth, Paul, Moore, P., Summerhayes, P., Escott-Price, Valentina ORCID: https://orcid.org/0000-0003-1784-5483, Foy, C., Archer, N., Hamilton, B.A., Lovestone, S., Powell, J., Brayne, C., Rubinsztein, D.C., Jones, Lesley ORCID: https://orcid.org/0000-0002-3007-4612, O'Donovan, Michael Conlon ORCID: https://orcid.org/0000-0001-7073-2379, Owen, Michael John ORCID: https://orcid.org/0000-0003-4798-0862 and Williams, Julie ORCID: https://orcid.org/0000-0002-4069-0259 2007. Interaction between theADAM12 andSH3MD1 genes may confer susceptibility to late-onset Alzheimer's disease. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics 144B (4) , pp. 448-452. 10.1002/ajmg.b.30456

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Abstract

The neuropathology of Alzheimer's disease (AD) is characterized by intracellular neurofibrillary tangles and the extracellular deposition of beta-amyloid (Abeta) in senile plaques. Abeta has been shown to mediate neurodegenerative and inflammatory changes associated with amyloid plaques, although the pathological mechanism of Abeta remains largely unknown. Recent evidence suggests that the FISH adapter protein binds to, and potentially regulates, ADAM12 (a disintegrin and metalloprotease 12) to mediate a neurotoxic effect of Abeta. The ADAM12 gene lies on chromosome 10q26.3, and the gene encoding FISH, SH3MD1, lies within a region of linkage to late-onset AD (LOAD) on 10q25.1. This study investigates whether there is a relationship between variation in ADAM12 and SH3MD1 and susceptibility to LOAD in a sample of 1,051 AD cases and 1,269 matched controls. We observe significant interactions between variants in the two genes that may influence susceptibility to LOAD. The most significant statistical interaction is between rs3740473, a synonymous single nucleotide polymorphism (SNP) in SH3MD1 and rs11244787, an intronic SNP in ADAM12 (effect size = 2.1 for interaction term, P = 0.006).

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG) Medicine Neuroscience and Mental Health Research Institute (NMHRI)
Subjects:	R Medicine > R Medicine (General)
Publisher:	Wiley-Blackwell
ISSN:	1552-4841
Last Modified:	04 Mar 2023 03:03
URI:	https://orca.cardiff.ac.uk/id/eprint/83096

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