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
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
2011 Impact Factor: 3.705
2011 SCImago Journal Rankings: 0.288
DOIhttp://dx.doi.org/10.1002/ajmg.b.30525
ReferencesReferences in Scopus
DC Field
Value
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
2011 Impact Factor: 3.705
2011 SCImago Journal Rankings: 0.288
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
Author Affiliations
  1. The University of Hong Kong
  2. Sun Yat-Sen University