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No association of a non‐synonymous PLAU polymorphism with Alzheimer's disease and disease‐related traits
Author(s) -
Papassotiropoulos Andreas,
Tsolaki Magdalini,
Wollmer M. Axel,
Molyva Dimitra,
Thal Dietmar R.,
Huynh KimDung,
Tracy Jay,
Staehelin Hannes B.,
Monsch Andreas U.,
Nitsch Roger M.,
Hock Christoph
Publication year - 2004
Publication title -
american journal of medical genetics part b: neuropsychiatric genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.393
H-Index - 126
eISSN - 1552-485X
pISSN - 1552-4841
DOI - 10.1002/ajmg.b.30103
Subject(s) - snp , single nucleotide polymorphism , genetics , biology , genetic association , alzheimer's disease , gene , allele , tag snp , disease , genotype , medicine
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 β‐amyloid peptide 1–42 (Aβ42). The PLAU gene, which is involved in the production and degradation of Aβ42, 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 Aβ, we also determined the levels of Aβ 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 β‐amyloid load in the medial temporal lobe or Aβ42 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. © 2004 Wiley‐Liss, Inc.