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Article: TTF-1 and RET promoter SNPs: Regulation of RET transcription in Hirschsprung's disease

TitleTTF-1 and RET promoter SNPs: Regulation of RET transcription in Hirschsprung's disease
Authors
Issue Date2005
PublisherOxford University Press. The Journal's web site is located at http://hmg.oxfordjournals.org/
Citation
Human Molecular Genetics, 2005, v. 14 n. 2, p. 191-204 How to Cite?
AbstractSingle nucleotide polymorphisms (SNPs) of the coding regions of receptor tyrosine kinase gene (RET) are associated with Hirschsprung's disease (HSCR, aganglionic megacolon). These SNPs, individually or combined, may act as a low penetrance susceptibility locus and/or be in linkage disequilibrium (LD) with another susceptibility locus located in RET regulatory regions. Because two RET promoter SNPs have been found associated with HSCR, in LD with HSCR-associated RET coding region haplotypes, their implication in the transcriptional regulation of RET is of major interest. Analysis of 172 sporadic HSCR patients also revealed the presence of HSCR-associated RET promoter SNPs in LD with the main coding region RET haplotype observed in Chinese patients. By using a weighted logistic regression approach, we determined that of all SNPs tested in our study, the promoter SNPs are the most correlated to the disease. Functional analysis of the RET promoter SNPs in the context of additional 5′ regulatory regions demonstrated that the HSCR-associated alleles decrease RET transcription. These SNPs overlap a TTF-1 binding site and TTF-1-activated RET transcription is also decreased by the HSCR-associated SNPs. Moreover, we identified an HSCR patient with a Gly322Ser TTF-1 mutation that compromises activation of transcription from HSCR-associated RET promoter haplotypes. Interestingly, we show that the pattern of RET and TTF-1 expression is coincident in developing human gut. We also present a detailed profile of the RET gene in our population, which provides an insight into the higher incidence of the disease in China. © Oxford University Press 2005; all rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/67999
ISSN
2015 Impact Factor: 5.985
2015 SCImago Journal Rankings: 4.288
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorGarciaBarcelo, Men_HK
dc.contributor.authorGanster, RWen_HK
dc.contributor.authorLui, VCHen_HK
dc.contributor.authorLeon, TYYen_HK
dc.contributor.authorSo, MTen_HK
dc.contributor.authorLau, AMFen_HK
dc.contributor.authorFu, Men_HK
dc.contributor.authorSham, MHen_HK
dc.contributor.authorKnight, Jen_HK
dc.contributor.authorZannini, MSen_HK
dc.contributor.authorSham, PCen_HK
dc.contributor.authorTam, PKHen_HK
dc.date.accessioned2010-09-06T06:00:21Z-
dc.date.available2010-09-06T06:00:21Z-
dc.date.issued2005en_HK
dc.identifier.citationHuman Molecular Genetics, 2005, v. 14 n. 2, p. 191-204en_HK
dc.identifier.issn0964-6906en_HK
dc.identifier.urihttp://hdl.handle.net/10722/67999-
dc.description.abstractSingle nucleotide polymorphisms (SNPs) of the coding regions of receptor tyrosine kinase gene (RET) are associated with Hirschsprung's disease (HSCR, aganglionic megacolon). These SNPs, individually or combined, may act as a low penetrance susceptibility locus and/or be in linkage disequilibrium (LD) with another susceptibility locus located in RET regulatory regions. Because two RET promoter SNPs have been found associated with HSCR, in LD with HSCR-associated RET coding region haplotypes, their implication in the transcriptional regulation of RET is of major interest. Analysis of 172 sporadic HSCR patients also revealed the presence of HSCR-associated RET promoter SNPs in LD with the main coding region RET haplotype observed in Chinese patients. By using a weighted logistic regression approach, we determined that of all SNPs tested in our study, the promoter SNPs are the most correlated to the disease. Functional analysis of the RET promoter SNPs in the context of additional 5′ regulatory regions demonstrated that the HSCR-associated alleles decrease RET transcription. These SNPs overlap a TTF-1 binding site and TTF-1-activated RET transcription is also decreased by the HSCR-associated SNPs. Moreover, we identified an HSCR patient with a Gly322Ser TTF-1 mutation that compromises activation of transcription from HSCR-associated RET promoter haplotypes. Interestingly, we show that the pattern of RET and TTF-1 expression is coincident in developing human gut. We also present a detailed profile of the RET gene in our population, which provides an insight into the higher incidence of the disease in China. © Oxford University Press 2005; all rights reserved.en_HK
dc.languageengen_HK
dc.publisherOxford University Press. The Journal's web site is located at http://hmg.oxfordjournals.org/en_HK
dc.relation.ispartofHuman Molecular Geneticsen_HK
dc.rightsHuman Molecular Genetics. Copyright © Oxford University Press.en_HK
dc.subject.meshAllelesen_HK
dc.subject.meshGene Expression Regulation - physiologyen_HK
dc.subject.meshHirschsprung Disease - genetics - metabolismen_HK
dc.subject.meshHumansen_HK
dc.subject.meshNuclear Proteins - genetics - metabolismen_HK
dc.subject.meshOncogene Proteins - genetics - metabolismen_HK
dc.subject.meshPolymorphism, Single Nucleotideen_HK
dc.subject.meshPromoter Regions, Geneticen_HK
dc.subject.meshProto-Oncogene Proteins c-reten_HK
dc.subject.meshReceptor Protein-Tyrosine Kinases - genetics - metabolismen_HK
dc.subject.meshSequence Analysis, DNAen_HK
dc.subject.meshTranscription Factors - genetics - metabolismen_HK
dc.titleTTF-1 and RET promoter SNPs: Regulation of RET transcription in Hirschsprung's diseaseen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0964-6906&volume=14&issue=2&spage=191&epage=204&date=2005&atitle=TTF-1+and+RET+promoter+SNPs:+regulation+of+RET+transcription+in+Hirschsprung%27s+diseaseen_HK
dc.identifier.emailGarciaBarcelo, M: mmgarcia@hku.hken_HK
dc.identifier.emailLui, VCH: vchlui@hku.hken_HK
dc.identifier.emailSham, MH: mhsham@hku.hken_HK
dc.identifier.emailSham, PC: pcsham@hku.hken_HK
dc.identifier.emailTam, PKH: paultam@hku.hken_HK
dc.identifier.authorityGarciaBarcelo, M=rp00445en_HK
dc.identifier.authorityLui, VCH=rp00363en_HK
dc.identifier.authoritySham, MH=rp00380en_HK
dc.identifier.authoritySham, PC=rp00459en_HK
dc.identifier.authorityTam, PKH=rp00060en_HK
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1093/hmg/ddi015en_HK
dc.identifier.pmid15548547-
dc.identifier.scopuseid_2-s2.0-19944430369en_HK
dc.identifier.hkuros97051en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-19944430369&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume14en_HK
dc.identifier.issue2en_HK
dc.identifier.spage191en_HK
dc.identifier.epage204en_HK
dc.identifier.isiWOS:000226199400002-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridGarciaBarcelo, M=6701767303en_HK
dc.identifier.scopusauthoridGanster, RW=6602083865en_HK
dc.identifier.scopusauthoridLui, VCH=7004231344en_HK
dc.identifier.scopusauthoridLeon, TYY=10641704600en_HK
dc.identifier.scopusauthoridSo, MT=8748542200en_HK
dc.identifier.scopusauthoridLau, AMF=16637678000en_HK
dc.identifier.scopusauthoridFu, M=49761323800en_HK
dc.identifier.scopusauthoridSham, MH=7003729109en_HK
dc.identifier.scopusauthoridKnight, J=13002769800en_HK
dc.identifier.scopusauthoridZannini, MS=55402080200en_HK
dc.identifier.scopusauthoridSham, PC=34573429300en_HK
dc.identifier.scopusauthoridTam, PKH=7202539421en_HK
dc.identifier.citeulike75242-

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