Linked Life Data

17510949

Source:http://linkedlifedata.com/resource/pubmed/id/17510949

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2007-11-20
pubmed:abstractText
Recent genetic studies have shown that variants of the ATP-binding cassette transporter A1, ABCA1, may be implicated in the pathogenesis of Alzheimer's disease (AD). In this case-control study, a panel of 19 single nucleotide polymorphisms (SNP) (including three amino-acid-coding SNPs used for replication of previous work, and 16 newly selected intronic tag SNPs) was genotyped. Nominally significant single marker P-values were observed in four SNPs, with the highest score of 0.003 for rs2297404 (OR = 1.88, 95%CI 1.23-2.87). In addition, six distinct linkage disequilibrium (LD) blocks were detected. LD block1 harbored three nominally significant SNPs (rs2297404, rs2230808, and rs2020927), and showed a different haplotype structure in the affected and unaffected groups. Of the four haplotypes identified, haplotype2 (CAC) was more prevalent in the disease group (0.323 in AD vs. 0.202 in control); while haplotype1 (TGG) was over-represented in the healthy controls (0.595 in control vs. 0.493 in AD), indicating disease risk conferring possibility of haplotype2. After doubling the sample size, the three nominally significant SNPs were still significantly associated with AD. Although coding SNP (rs2230808) was confirmed to have a significant association with AD, prediction of the effects of an amino acid substitution SNP rs2230808 (R1587K) on the three-dimensional structure and function of the ABCA1 protein using PolyPhen program revealed that it is unlikely to be functionally significant. However, the adjacent rs2297404 in the same LD block is potentially functionally significant because of its position in the immediate vicinity of a splicing branch site. Further functional analysis of this polymorphism should be a high priority.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1552-485X
pubmed:author
pubmed:copyrightInfo
2007 Wiley-Liss, Inc.
pubmed:issnType
Electronic
pubmed:day
5
pubmed:volume
144B
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1007-13
pubmed:dateRevised
2008-5-21
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
A novel intronic polymorphism of ABCA1 gene reveals risk for sporadic Alzheimer's disease in Chinese.
pubmed:affiliation
Department of Medicine, The University of Hong Kong, Hong Kong.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't