Association of late-onset Alzheimer disease with a genotype of PLAU, the gene encoding urokinase-type plasminogen activator on chromosome 10q22.2

U. Finckh, K. Van Hadeln, T. Müller-Thomsen, A. Alberici, G. Binetti, C. Hock, R. M. Nitsch, G. Stoppe, J. Reiss, A. Gal

Research output: Contribution to journalArticle

Abstract

Urokinase-type plasminogen activator (uPA) converts plasminogen to plasmin. Plasmin is involved in processing of amyloid precursor protein and degrades secreted and aggregated amyloid-β, a hallmark of Alzheimer disease (AD). PLAU, the gene encoding uPA, maps to chromosome 10q22.2 between two regions showing linkage to late-onset AD (LOAD). We genotyped a frequent C/T single nucleotide polymorphism in codon 141 of PLAU (P141L) in 347 patients with LOAD and 291 control subjects, LOAD was associated with homozygous C/C PLAU genotype in the whole sample (χ2=15.7, P=0.00039, df 2), as well as in all sub-samples stratified by gender or APOE ε4 carrier status (χ 2≥ 6.84, P≤0.033, df 2). Odds ratio for LOAD due to homozygosity C/C was 1.89 (95% confidence interval 1.37-2,61). PLAU is a promising new candidate gene for LOAD, with allele C (P141) being a recessive risk allele or allele T (L141) conferring protection.

Original languageEnglish
Pages (from-to)213-217
Number of pages5
JournalNeurogenetics
Volume4
Issue number4
DOIs
Publication statusPublished - Aug 2003

Keywords

  • Alzheimer disease
  • APOE
  • Plasmin
  • Urokinase gene

ASJC Scopus subject areas

  • Genetics(clinical)
  • Neuroscience(all)

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    Finckh, U., Van Hadeln, K., Müller-Thomsen, T., Alberici, A., Binetti, G., Hock, C., Nitsch, R. M., Stoppe, G., Reiss, J., & Gal, A. (2003). Association of late-onset Alzheimer disease with a genotype of PLAU, the gene encoding urokinase-type plasminogen activator on chromosome 10q22.2. Neurogenetics, 4(4), 213-217. https://doi.org/10.1007/s10048-003-0157-9