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- Publisher Website: 10.1002/ajmg.b.30525
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- PMID: 17510949
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Article: A novel intronic polymorphism of ABCA1 gene reveals risk for sporadic Alzheimer's disease in Chinese
Title | A novel intronic polymorphism of ABCA1 gene reveals risk for sporadic Alzheimer's disease in Chinese |
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Authors | |
Keywords | ABCA1 Alzheimer's disease Association Case-control Haplotype Single nucleotide polymorphisms (SNP) |
Issue Date | 2007 |
Publisher | John 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? |
Abstract | 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 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 Identifier | http://hdl.handle.net/10722/91481 |
ISSN | 2023 Impact Factor: 1.6 2023 SCImago Journal Rankings: 1.228 |
ISI Accession Number ID | |
References |
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Leung, WC | en_HK |
dc.contributor.author | Li, Y | en_HK |
dc.contributor.author | Li, Z | en_HK |
dc.contributor.author | Tang, AYB | en_HK |
dc.contributor.author | Cheung, BMY | en_HK |
dc.contributor.author | Leung, RYH | en_HK |
dc.contributor.author | Yik, PY | en_HK |
dc.contributor.author | Jin, DY | en_HK |
dc.contributor.author | Song, YQ | en_HK |
dc.date.accessioned | 2010-09-17T10:20:07Z | - |
dc.date.available | 2010-09-17T10:20:07Z | - |
dc.date.issued | 2007 | en_HK |
dc.identifier.citation | American Journal Of Medical Genetics, Part B: Neuropsychiatric Genetics, 2007, v. 144 n. 8, p. 1007-1013 | en_HK |
dc.identifier.issn | 1552-4841 | en_HK |
dc.identifier.uri | http://hdl.handle.net/10722/91481 | - |
dc.description.abstract | 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 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.language | eng | en_HK |
dc.publisher | John Wiley & Sons, Inc. The Journal's web site is located at http://www.interscience.wiley.com/jpages/0148-7299:1/ | en_HK |
dc.relation.ispartof | American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics | en_HK |
dc.subject | ABCA1 | en_HK |
dc.subject | Alzheimer's disease | en_HK |
dc.subject | Association | en_HK |
dc.subject | Case-control | en_HK |
dc.subject | Haplotype | en_HK |
dc.subject | Single nucleotide polymorphisms (SNP) | en_HK |
dc.subject.mesh | ATP-Binding Cassette Transporters - genetics | en_HK |
dc.subject.mesh | Age of Onset | en_HK |
dc.subject.mesh | Aged | en_HK |
dc.subject.mesh | Aged, 80 and over | en_HK |
dc.subject.mesh | Alzheimer Disease - diagnosis - epidemiology - genetics | en_HK |
dc.subject.mesh | Asian Continental Ancestry Group - genetics | en_HK |
dc.subject.mesh | Case-Control Studies | en_HK |
dc.subject.mesh | China - epidemiology | en_HK |
dc.subject.mesh | Female | en_HK |
dc.subject.mesh | Genetic Predisposition to Disease | en_HK |
dc.subject.mesh | Haplotypes | en_HK |
dc.subject.mesh | Humans | en_HK |
dc.subject.mesh | Introns - genetics | en_HK |
dc.subject.mesh | Linkage Disequilibrium | en_HK |
dc.subject.mesh | Male | en_HK |
dc.subject.mesh | Polymorphism, Single Nucleotide | en_HK |
dc.subject.mesh | Quantitative Trait, Heritable | en_HK |
dc.title | A novel intronic polymorphism of ABCA1 gene reveals risk for sporadic Alzheimer's disease in Chinese | en_HK |
dc.type | Article | en_HK |
dc.identifier.email | Cheung, BMY:mycheung@hku.hk | en_HK |
dc.identifier.email | Jin, DY:dyjin@hkucc.hku.hk | en_HK |
dc.identifier.email | Song, YQ:songy@hkucc.hku.hk | en_HK |
dc.identifier.authority | Cheung, BMY=rp01321 | en_HK |
dc.identifier.authority | Jin, DY=rp00452 | en_HK |
dc.identifier.authority | Song, YQ=rp00488 | en_HK |
dc.description.nature | link_to_subscribed_fulltext | - |
dc.identifier.doi | 10.1002/ajmg.b.30525 | en_HK |
dc.identifier.pmid | 17510949 | - |
dc.identifier.scopus | eid_2-s2.0-36749014486 | en_HK |
dc.identifier.hkuros | 140830 | - |
dc.relation.references | http://www.scopus.com/mlt/select.url?eid=2-s2.0-36749014486&selection=ref&src=s&origin=recordpage | en_HK |
dc.identifier.volume | 144 | en_HK |
dc.identifier.issue | 8 | en_HK |
dc.identifier.spage | 1007 | en_HK |
dc.identifier.epage | 1013 | en_HK |
dc.identifier.eissn | 1552-485X | - |
dc.identifier.isi | WOS:000251096700008 | - |
dc.publisher.place | United States | en_HK |
dc.identifier.scopusauthorid | Leung, WC=23028053200 | en_HK |
dc.identifier.scopusauthorid | Li, Y=36078824800 | en_HK |
dc.identifier.scopusauthorid | Li, Z=26642887400 | en_HK |
dc.identifier.scopusauthorid | Tang, AYB=23029183800 | en_HK |
dc.identifier.scopusauthorid | Cheung, BMY=7103294806 | en_HK |
dc.identifier.scopusauthorid | Leung, RYH=7101876102 | en_HK |
dc.identifier.scopusauthorid | Yik, PY=15060623700 | en_HK |
dc.identifier.scopusauthorid | Jin, DY=7201973614 | en_HK |
dc.identifier.scopusauthorid | Song, YQ=7404921212 | en_HK |
dc.identifier.issnl | 1552-4841 | - |