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Article: A novel intronic polymorphism of ABCA1 gene reveals risk for sporadic Alzheimer's disease in Chinese
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TitleA novel intronic polymorphism of ABCA1 gene reveals risk for sporadic Alzheimer's disease in Chinese
 
AuthorsLeung, WC1
Li, Y1
Li, Z1 2
Tang, AYB1
Cheung, BMY1
Leung, RYH1
Yik, PY1
Jin, DY1
Song, YQ1 1 1 1
 
KeywordsABCA1
Alzheimer's disease
Association
Case-control
Haplotype
Single nucleotide polymorphisms (SNP)
 
Issue Date2007
 
PublisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www.interscience.wiley.com/jpages/0148-7299:1/
 
CitationAmerican Journal Of Medical Genetics, Part B: Neuropsychiatric Genetics, 2007, v. 144 n. 8, p. 1007-1013 [How to Cite?]
DOI: http://dx.doi.org/10.1002/ajmg.b.30525
 
AbstractRecent 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 Poly-Phen 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. © 2007 Wiley-Liss, Inc.
 
ISSN1552-4841
2012 Impact Factor: 3.231
2012 SCImago Journal Rankings: 1.406
 
DOIhttp://dx.doi.org/10.1002/ajmg.b.30525
 
ISI Accession Number IDWOS:000251096700008
 
ReferencesReferences in Scopus
 
DC FieldValue
dc.contributor.authorLeung, WC
 
dc.contributor.authorLi, Y
 
dc.contributor.authorLi, Z
 
dc.contributor.authorTang, AYB
 
dc.contributor.authorCheung, BMY
 
dc.contributor.authorLeung, RYH
 
dc.contributor.authorYik, PY
 
dc.contributor.authorJin, DY
 
dc.contributor.authorSong, YQ
 
dc.date.accessioned2010-09-17T10:20:07Z
 
dc.date.available2010-09-17T10:20:07Z
 
dc.date.issued2007
 
dc.description.abstractRecent 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 Poly-Phen 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. © 2007 Wiley-Liss, Inc.
 
dc.description.natureLink_to_subscribed_fulltext
 
dc.identifier.citationAmerican Journal Of Medical Genetics, Part B: Neuropsychiatric Genetics, 2007, v. 144 n. 8, p. 1007-1013 [How to Cite?]
DOI: http://dx.doi.org/10.1002/ajmg.b.30525
 
dc.identifier.doihttp://dx.doi.org/10.1002/ajmg.b.30525
 
dc.identifier.eissn1552-485X
 
dc.identifier.epage1013
 
dc.identifier.hkuros140830
 
dc.identifier.isiWOS:000251096700008
 
dc.identifier.issn1552-4841
2012 Impact Factor: 3.231
2012 SCImago Journal Rankings: 1.406
 
dc.identifier.issue8
 
dc.identifier.pmid17510949
 
dc.identifier.scopuseid_2-s2.0-36749014486
 
dc.identifier.spage1007
 
dc.identifier.urihttp://hdl.handle.net/10722/91481
 
dc.identifier.volume144
 
dc.languageeng
 
dc.publisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www.interscience.wiley.com/jpages/0148-7299:1/
 
dc.publisher.placeUnited States
 
dc.relation.ispartofAmerican Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
 
dc.relation.referencesReferences in Scopus
 
dc.subject.meshATP-Binding Cassette Transporters - genetics
 
dc.subject.meshAge of Onset
 
dc.subject.meshAged
 
dc.subject.meshAged, 80 and over
 
dc.subject.meshAlzheimer Disease - diagnosis - epidemiology - genetics
 
dc.subject.meshAsian Continental Ancestry Group - genetics
 
dc.subject.meshCase-Control Studies
 
dc.subject.meshChina - epidemiology
 
dc.subject.meshFemale
 
dc.subject.meshGenetic Predisposition to Disease
 
dc.subject.meshHaplotypes
 
dc.subject.meshHumans
 
dc.subject.meshIntrons - genetics
 
dc.subject.meshLinkage Disequilibrium
 
dc.subject.meshMale
 
dc.subject.meshPolymorphism, Single Nucleotide
 
dc.subject.meshQuantitative Trait, Heritable
 
dc.subjectABCA1
 
dc.subjectAlzheimer's disease
 
dc.subjectAssociation
 
dc.subjectCase-control
 
dc.subjectHaplotype
 
dc.subjectSingle nucleotide polymorphisms (SNP)
 
dc.titleA novel intronic polymorphism of ABCA1 gene reveals risk for sporadic Alzheimer's disease in Chinese
 
dc.typeArticle
 
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Author Affiliations
  1. The University of Hong Kong
  2. Sun Yat-Sen University