File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)
Supplementary

Article: CYP46A1 functional promoter haplotypes decipher genetic susceptibility to Alzheimer's disease

TitleCYP46A1 functional promoter haplotypes decipher genetic susceptibility to Alzheimer's disease
Authors
Issue Date2010
PublisherI O S Press. The Journal's web site is located at http://www.iospress.nl/html/13872877.php
Citation
Journal Of Alzheimer's Disease, 2010, v. 21 n. 4, p. 1311-1323 How to Cite?
AbstractWe here demonstrate that promoter polymorphisms rs8003602 and rs3783320 of cholesterol 24S-hydroxylase (CYP46A1) were significantly associated with Alzheimer's disease (AD) in Chinese subjects. Haplotype analyses showed that haplotype CG is the risk haplotype. Either single marker or haplotypic association was found only in the APOE ε4 negative group. The association was then replicated in an independent set of case-control samples in Mongolians. We also investigated the function of promoter haplotypes and found that luciferase expression for TA promoter construct exhibited significantly higher expression level than the risk CG promoter construct. This finding might indicate individuals bearing the CG haplotype are genetically more susceptible to AD compared to those with TA haplotype. Further, we found MYT1 could be the potential transcription factor binding to the significant promoter polymorphism and mediated gene transcriptional activity. In general, our results show that promoter haplotypes could significantly affect CYP46A1 gene transcription level possibly through interacting with certain transcription factors. © 2010 IOS Press and the authors. All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/129092
ISSN
2015 Impact Factor: 3.92
2015 SCImago Journal Rankings: 1.774
ISI Accession Number ID
Funding AgencyGrant Number
University of Hong Kong
Funding Information:

We thank all individuals that contributed to this work, including those who helped with sample collecting, DNA extraction, and APOE genotyping. Special thanks should go to Prof. Hudson who generously provided us with the MYT1 plasmids. We would like to thank all technicians in our department for their technical support, especially Jess who had shared her expertise in purifying the Myt1 proteins. The authors are also thankful for technicians in Genome Research Centre, HKU who had helped a lot in SEQUENOM MassARRAY. This work was supported by seeding grant from The University of Hong Kong.

References

 

DC FieldValueLanguage
dc.contributor.authorLi, Yen_HK
dc.contributor.authorChu, LWen_HK
dc.contributor.authorWang, Ben_HK
dc.contributor.authorYik, PYen_HK
dc.contributor.authorHuriletemueren_HK
dc.contributor.authorJin, DYen_HK
dc.contributor.authorMa, Xen_HK
dc.contributor.authorSong, YQen_HK
dc.date.accessioned2010-12-23T08:32:24Z-
dc.date.available2010-12-23T08:32:24Z-
dc.date.issued2010en_HK
dc.identifier.citationJournal Of Alzheimer's Disease, 2010, v. 21 n. 4, p. 1311-1323en_HK
dc.identifier.issn1387-2877en_HK
dc.identifier.urihttp://hdl.handle.net/10722/129092-
dc.description.abstractWe here demonstrate that promoter polymorphisms rs8003602 and rs3783320 of cholesterol 24S-hydroxylase (CYP46A1) were significantly associated with Alzheimer's disease (AD) in Chinese subjects. Haplotype analyses showed that haplotype CG is the risk haplotype. Either single marker or haplotypic association was found only in the APOE ε4 negative group. The association was then replicated in an independent set of case-control samples in Mongolians. We also investigated the function of promoter haplotypes and found that luciferase expression for TA promoter construct exhibited significantly higher expression level than the risk CG promoter construct. This finding might indicate individuals bearing the CG haplotype are genetically more susceptible to AD compared to those with TA haplotype. Further, we found MYT1 could be the potential transcription factor binding to the significant promoter polymorphism and mediated gene transcriptional activity. In general, our results show that promoter haplotypes could significantly affect CYP46A1 gene transcription level possibly through interacting with certain transcription factors. © 2010 IOS Press and the authors. All rights reserved.en_HK
dc.languageengen_US
dc.publisherI O S Press. The Journal's web site is located at http://www.iospress.nl/html/13872877.phpen_HK
dc.relation.ispartofJournal of Alzheimer's Diseaseen_HK
dc.subject.meshAgeden_HK
dc.subject.meshAged, 80 and overen_HK
dc.subject.meshAlzheimer Disease - diagnosis - enzymology - geneticsen_HK
dc.subject.meshAsian Continental Ancestry Group - geneticsen_HK
dc.subject.meshCase-Control Studiesen_HK
dc.subject.meshFemaleen_HK
dc.subject.meshGenetic Predisposition to Disease - geneticsen_HK
dc.subject.meshHaplotypes - geneticsen_HK
dc.subject.meshHumansen_HK
dc.subject.meshMaleen_HK
dc.subject.meshMiddle Ageden_HK
dc.subject.meshPolymorphism, Single Nucleotide - geneticsen_HK
dc.subject.meshPromoter Regions, Genetic - geneticsen_HK
dc.subject.meshRisk Factorsen_HK
dc.subject.meshSteroid Hydroxylases - geneticsen_HK
dc.titleCYP46A1 functional promoter haplotypes decipher genetic susceptibility to Alzheimer's diseaseen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=1387-2877&volume=&spage=&epage=&date=2010&atitle=Cyp46a1+Functional+Promoter+Haplotypes+Decipher+Genetic+Susceptibility+To+Alzheimer%27s+Diseaseen_US
dc.identifier.emailJin, DY:dyjin@hkucc.hku.hken_HK
dc.identifier.emailSong, YQ:songy@hkucc.hku.hken_HK
dc.identifier.authorityJin, DY=rp00452en_HK
dc.identifier.authoritySong, YQ=rp00488en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.3233/JAD-2010-100765en_HK
dc.identifier.pmid20693622en_HK
dc.identifier.scopuseid_2-s2.0-78650458614en_HK
dc.identifier.hkuros178532en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-78650458614&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume21en_HK
dc.identifier.issue4en_HK
dc.identifier.spage1311en_HK
dc.identifier.epage1323en_HK
dc.identifier.isiWOS:000283049700023-
dc.publisher.placeNetherlandsen_HK
dc.identifier.scopusauthoridLi, Y=36078298200en_HK
dc.identifier.scopusauthoridChu, LW=7202236665en_HK
dc.identifier.scopusauthoridWang, B=23104530700en_HK
dc.identifier.scopusauthoridYik, PY=15060623700en_HK
dc.identifier.scopusauthoridHuriletemuer=36833784000en_HK
dc.identifier.scopusauthoridJin, DY=7201973614en_HK
dc.identifier.scopusauthoridMa, X=35196580300en_HK
dc.identifier.scopusauthoridSong, YQ=7404921212en_HK

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats