File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)
Supplementary

Article: A novel intronic polymorphism of ABCA1 gene reveals risk for sporadic Alzheimer's disease in Chinese

TitleA novel intronic polymorphism of ABCA1 gene reveals risk for sporadic Alzheimer's disease in Chinese
Authors
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/
Citation
American Journal Of Medical Genetics, Part B: Neuropsychiatric Genetics, 2007, v. 144 n. 8, p. 1007-1013 How to Cite?
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.
Persistent Identifierhttp://hdl.handle.net/10722/91481
ISSN
2014 Impact Factor: 3.416
2014 SCImago Journal Rankings: 1.643
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorLeung, WCen_HK
dc.contributor.authorLi, Yen_HK
dc.contributor.authorLi, Zen_HK
dc.contributor.authorTang, AYBen_HK
dc.contributor.authorCheung, BMYen_HK
dc.contributor.authorLeung, RYHen_HK
dc.contributor.authorYik, PYen_HK
dc.contributor.authorJin, DYen_HK
dc.contributor.authorSong, YQen_HK
dc.date.accessioned2010-09-17T10:20:07Z-
dc.date.available2010-09-17T10:20:07Z-
dc.date.issued2007en_HK
dc.identifier.citationAmerican Journal Of Medical Genetics, Part B: Neuropsychiatric Genetics, 2007, v. 144 n. 8, p. 1007-1013en_HK
dc.identifier.issn1552-4841en_HK
dc.identifier.urihttp://hdl.handle.net/10722/91481-
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.en_HK
dc.languageengen_HK
dc.publisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www.interscience.wiley.com/jpages/0148-7299:1/en_HK
dc.relation.ispartofAmerican Journal of Medical Genetics, Part B: Neuropsychiatric Geneticsen_HK
dc.subjectABCA1en_HK
dc.subjectAlzheimer's diseaseen_HK
dc.subjectAssociationen_HK
dc.subjectCase-controlen_HK
dc.subjectHaplotypeen_HK
dc.subjectSingle nucleotide polymorphisms (SNP)en_HK
dc.subject.meshATP-Binding Cassette Transporters - geneticsen_HK
dc.subject.meshAge of Onseten_HK
dc.subject.meshAgeden_HK
dc.subject.meshAged, 80 and overen_HK
dc.subject.meshAlzheimer Disease - diagnosis - epidemiology - geneticsen_HK
dc.subject.meshAsian Continental Ancestry Group - geneticsen_HK
dc.subject.meshCase-Control Studiesen_HK
dc.subject.meshChina - epidemiologyen_HK
dc.subject.meshFemaleen_HK
dc.subject.meshGenetic Predisposition to Diseaseen_HK
dc.subject.meshHaplotypesen_HK
dc.subject.meshHumansen_HK
dc.subject.meshIntrons - geneticsen_HK
dc.subject.meshLinkage Disequilibriumen_HK
dc.subject.meshMaleen_HK
dc.subject.meshPolymorphism, Single Nucleotideen_HK
dc.subject.meshQuantitative Trait, Heritableen_HK
dc.titleA novel intronic polymorphism of ABCA1 gene reveals risk for sporadic Alzheimer's disease in Chineseen_HK
dc.typeArticleen_HK
dc.identifier.emailCheung, BMY:mycheung@hku.hken_HK
dc.identifier.emailJin, DY:dyjin@hkucc.hku.hken_HK
dc.identifier.emailSong, YQ:songy@hkucc.hku.hken_HK
dc.identifier.authorityCheung, BMY=rp01321en_HK
dc.identifier.authorityJin, DY=rp00452en_HK
dc.identifier.authoritySong, YQ=rp00488en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1002/ajmg.b.30525en_HK
dc.identifier.pmid17510949-
dc.identifier.scopuseid_2-s2.0-36749014486en_HK
dc.identifier.hkuros140830-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-36749014486&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume144en_HK
dc.identifier.issue8en_HK
dc.identifier.spage1007en_HK
dc.identifier.epage1013en_HK
dc.identifier.eissn1552-485X-
dc.identifier.isiWOS:000251096700008-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridLeung, WC=23028053200en_HK
dc.identifier.scopusauthoridLi, Y=36078824800en_HK
dc.identifier.scopusauthoridLi, Z=26642887400en_HK
dc.identifier.scopusauthoridTang, AYB=23029183800en_HK
dc.identifier.scopusauthoridCheung, BMY=7103294806en_HK
dc.identifier.scopusauthoridLeung, RYH=7101876102en_HK
dc.identifier.scopusauthoridYik, PY=15060623700en_HK
dc.identifier.scopusauthoridJin, DY=7201973614en_HK
dc.identifier.scopusauthoridSong, YQ=7404921212en_HK

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats