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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
10
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pubmed:dateCreated |
2008-8-18
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pubmed:abstractText |
The gamma-secretase complex is a multimeric aspartyl protease which plays a pivotal role in the production of amyloid beta-peptide, the main component of senile plaques in Alzheimer's disease (AD). APH-1a and APH-1b have been recently identified as important subunits of the gamma-secretase complex. We previously studied sequence variations in both genes and their association with AD in a small Italian population. The rare polymorphism c + 651T > G in APH-1b showed a possible interaction with the Apolipoprotein E (APOE) epsilon4 allele in the AD population sample. We extended our genetic analysis to 449 AD patients and 435 controls and, in AD cases, we found a significant interaction (P=0.001) between the allelic variants in the two genes, resulting in a marked increase of the relative risk for AD (OR=28.6). Despite the amino acid substitution does not seem to modify either the intracellular localization or the half-life of APH-1b protein, these data suggest that a cooperative mechanism involving APOE and APH-1b plays a role in the susceptibility to develop AD.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
1558-1497
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pubmed:author |
pubmed-author:AlbertiniAlbertoA,
pubmed-author:BiunnoIdaI,
pubmed-author:DominiciRobertoR,
pubmed-author:FinazziDarioD,
pubmed-author:GalimbertiDanielaD,
pubmed-author:GattaLuisa BeneriniLB,
pubmed-author:LovatiCarloC,
pubmed-author:MarianiClaudioC,
pubmed-author:MusiccoMassimoM,
pubmed-author:PoliMauraM,
pubmed-author:ScarpiniElioE
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pubmed:issnType |
Electronic
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pubmed:volume |
29
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1494-501
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:17466415-Aged,
pubmed-meshheading:17466415-Alzheimer Disease,
pubmed-meshheading:17466415-Amino Acid Substitution,
pubmed-meshheading:17466415-Amyloid Precursor Protein Secretases,
pubmed-meshheading:17466415-Amyloid beta-Peptides,
pubmed-meshheading:17466415-Animals,
pubmed-meshheading:17466415-Apolipoprotein E4,
pubmed-meshheading:17466415-COS Cells,
pubmed-meshheading:17466415-Cercopithecus aethiops,
pubmed-meshheading:17466415-DNA Mutational Analysis,
pubmed-meshheading:17466415-Female,
pubmed-meshheading:17466415-Gene Frequency,
pubmed-meshheading:17466415-Genetic Predisposition to Disease,
pubmed-meshheading:17466415-Genetic Testing,
pubmed-meshheading:17466415-Genetic Variation,
pubmed-meshheading:17466415-Genotype,
pubmed-meshheading:17466415-HeLa Cells,
pubmed-meshheading:17466415-Humans,
pubmed-meshheading:17466415-Italy,
pubmed-meshheading:17466415-Male,
pubmed-meshheading:17466415-Membrane Proteins,
pubmed-meshheading:17466415-Middle Aged,
pubmed-meshheading:17466415-Mutation,
pubmed-meshheading:17466415-Peptide Hydrolases,
pubmed-meshheading:17466415-Polymorphism, Single Nucleotide,
pubmed-meshheading:17466415-Transfection
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pubmed:year |
2008
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pubmed:articleTitle |
Interaction between the APOE epsilon4 allele and the APH-1b c + 651T > G SNP in Alzheimer's disease.
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pubmed:affiliation |
Section of Chemistry, Faculty of Medicine, University of Brescia, viale Europa 11, 25123 Brescia, Italy.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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