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No association of a non-synonymous PLAU polymorphism with Alzheimer's disease and disease-related traits


Papassotiropoulos, A; Tsolaki, M; Wollmer, M A; Molyva, D; Thal, D R; Huynh, K D; Tracy, J; Staehelin, H B; Monsch, A U; Nitsch, R M; Hock, C (2005). No association of a non-synonymous PLAU polymorphism with Alzheimer's disease and disease-related traits. American Journal of Medical Genetics. Part B, 132B(1):21-23.

Abstract

A 30 cM broad genomic region on the long arm of chromosome 10 at 80 cM shows significant and consistent linkage with AD and with plasma concentration of the beta-amyloid peptide 1-42 (Abeta42). The PLAU gene, which is involved in the production and degradation of Abeta42, maps to that region and is therefore a strong positional candidate for association with sporadic AD. We analyzed the non-synonymous single nucleotide polymorphism (SNP) rs2227564 in two independent case-control series from Switzerland and Greece and investigated the influence of this SNP on cognition in elderly individuals. Because PLAU modulates the cleavage of the amyloid precursor protein (APP) and the degradation of Abeta, we also determined the levels of Abeta in the brain, plasma and in the cerebrospinal fluid (CSF). We found no evidence for association of this SNP with AD or with AD-related traits such as beta-amyloid load in the medial temporal lobe or Abeta42 concentration in the CSF and in plasma. Our findings do not support a major role of PLAU polymorphisms as susceptibility factors for AD and suggest that large-scale association studies which combine genetic information from populations with similar genetic background might prevent the generation of spurious associations. Although PLAU may be pathophysiologially related to AD, the contribution of common genetic variants of this gene to the risk for developing AD is likely to be low.

Abstract

A 30 cM broad genomic region on the long arm of chromosome 10 at 80 cM shows significant and consistent linkage with AD and with plasma concentration of the beta-amyloid peptide 1-42 (Abeta42). The PLAU gene, which is involved in the production and degradation of Abeta42, maps to that region and is therefore a strong positional candidate for association with sporadic AD. We analyzed the non-synonymous single nucleotide polymorphism (SNP) rs2227564 in two independent case-control series from Switzerland and Greece and investigated the influence of this SNP on cognition in elderly individuals. Because PLAU modulates the cleavage of the amyloid precursor protein (APP) and the degradation of Abeta, we also determined the levels of Abeta in the brain, plasma and in the cerebrospinal fluid (CSF). We found no evidence for association of this SNP with AD or with AD-related traits such as beta-amyloid load in the medial temporal lobe or Abeta42 concentration in the CSF and in plasma. Our findings do not support a major role of PLAU polymorphisms as susceptibility factors for AD and suggest that large-scale association studies which combine genetic information from populations with similar genetic background might prevent the generation of spurious associations. Although PLAU may be pathophysiologially related to AD, the contribution of common genetic variants of this gene to the risk for developing AD is likely to be low.

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11 citations in Web of Science®
10 citations in Scopus®
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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute for Regenerative Medicine (IREM)
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2005
Deposited On:02 Sep 2011 08:27
Last Modified:16 Aug 2016 10:14
Publisher:Wiley-Blackwell
ISSN:1552-4841
Publisher DOI:https://doi.org/10.1002/ajmg.b.30103
PubMed ID:15558716

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