Source:http://linkedlifedata.com/resource/pubmed/id/16023140
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
1-2
|
| pubmed:dateCreated |
2005-8-29
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| pubmed:abstractText |
Genetic linkage studies have provided evidence for a late-onset Alzheimer's disease (AD) susceptibility locus on chromosome 21q. We have tested, in a two-stage association study, whether allelic or haplotype variation of the beta-amyloid cleaving enzyme-2 (BACE2) locus on chromosome 21q affects the risk of late-onset AD. In stage-1, an unselected population-based sample of Finns aged 85 years or over (n=515) was analysed. Neuropathologic examination including beta-amyloid load quantification was possible in over 50% (n=264) of these subjects. AD patients (n=100) and controls (n=48) were defined by modified neuropathological NIA-RI criteria. Positive associations were taken as a hypothesis, and tested in stage-2 using 483 AD families from the USA. Four single nucleotide polymorphisms (SNPs) of BACE2 gene were tested in stage-1. A SNP close to exon-6 was associated with neuropathologically verified AD (p=0.02) and also with beta-amyloid load in non-selected autopsied subjects after conditioning with APOE genotype (p=0.001). In haplotype analysis a specific, relatively common haplotype (H5) was found to associate with AD (p=0.004) and a second haplotype (H7) showed a weaker association with protection against AD (p=0.04). In stage-2, the SNP association was not replicated, whereas the haplotype H5 association was replicated (p=0.004) and a trend to association was found with the putative protective haplotype H7 (two-sided p=0.08). BACE2 haplotype association with AD in two independent datasets provides further evidence for an AD susceptibility locus on chromosome 21q within or close to BACE2.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
Sep
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| pubmed:issn |
0022-510X
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| pubmed:author |
pubmed-author:AdighibeOmanmaO,
pubmed-author:ArepalliSampathS,
pubmed-author:ComptonDanielleD,
pubmed-author:EdlandSteven DSD,
pubmed-author:HaltiaMattiM,
pubmed-author:HardyJohnJ,
pubmed-author:MyllykangasLiisaL,
pubmed-author:NiinistöLeenaL,
pubmed-author:NotkolaIrma-LeenaIL,
pubmed-author:PolvikoskiTuomoT,
pubmed-author:SulkavaRaimoR,
pubmed-author:TienariPentti JPJ,
pubmed-author:Wavrant-De VrièzeFabienneF
|
| pubmed:issnType |
Print
|
| pubmed:day |
15
|
| pubmed:volume |
236
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
17-24
|
| pubmed:dateRevised |
2009-11-19
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| pubmed:meshHeading |
pubmed-meshheading:16023140-Aged,
pubmed-meshheading:16023140-Aged, 80 and over,
pubmed-meshheading:16023140-Alzheimer Disease,
pubmed-meshheading:16023140-Amyloid Precursor Protein Secretases,
pubmed-meshheading:16023140-Apolipoproteins E,
pubmed-meshheading:16023140-Aspartic Acid Endopeptidases,
pubmed-meshheading:16023140-Chi-Square Distribution,
pubmed-meshheading:16023140-Chromosomes, Human, Pair 21,
pubmed-meshheading:16023140-Databases as Topic,
pubmed-meshheading:16023140-Exons,
pubmed-meshheading:16023140-Female,
pubmed-meshheading:16023140-Genetic Predisposition to Disease,
pubmed-meshheading:16023140-Haplotypes,
pubmed-meshheading:16023140-Humans,
pubmed-meshheading:16023140-Male,
pubmed-meshheading:16023140-Neurologic Examination,
pubmed-meshheading:16023140-Polymorphism, Single Nucleotide
|
| pubmed:year |
2005
|
| pubmed:articleTitle |
Chromosome 21 BACE2 haplotype associates with Alzheimer's disease: a two-stage study.
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| pubmed:affiliation |
Department of Pathology, Helsinki University Central Hospital, Helsinki, Finland.
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| pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, Non-U.S. Gov't,
Multicenter Study
|