A genome-wide association study identifies GLT6D1 as a susceptibility locus for periodontitis
Identifieur interne : 004F12 ( Main/Exploration ); précédent : 004F11; suivant : 004F13A genome-wide association study identifies GLT6D1 as a susceptibility locus for periodontitis
Auteurs : Arne S. Schaefer [Allemagne] ; Gesa M. Richter ; Michael Nothnagel ; Thomas Manke ; Henrik Dommisch ; Gunnar Jacobs ; Alexander Arlt ; Philip Rosenstiel ; Barbara Noack ; Birte Groessner-Schreiber [Allemagne] ; S Ren Jepsen ; Bruno G. Loos [Pays-Bas] ; Stefan SchreiberSource :
- Human Molecular Genetics [ 0964-6906 ] ; 2010-02-01.
Abstract
Periodontitis is a widespread, complex inflammatory disease of the mouth, which results in a loss of gingival tissue and alveolar bone, with aggressive periodontitis (AgP) as its most severe form. To identify genetic risk factors for periodontitis, we conducted a genome-wide association study in German AgP patients. We found AgP to be strongly associated with the intronic SNP rs1537415, which is located in the glycosyltransferase gene GLT6D1. We replicated the association in a panel of Dutch generalized and localized AgP patients. In the combined analysis including 1758 subjects, rs1537415 reached a genome-wide significance level of P= 5.51 × 10−9, OR = 1.59 (95% CI 1.36–1.86). The associated rare G allele of rs1537415 showed an enrichment of 10% in periodontitis cases (48.4% in comparison with 38.8% in controls). Fine-mapping and a haplotype analysis indicated that rs1537415 showed the strongest association signal. Sequencing identified no further associated variant. Tissue-specific expression analysis of GLT6D1 indicated high transcript levels in the leukocytes, the gingiva and testis. Analysis of potential transcription factor binding sites at this locus predicted a significant reduction of GATA-3 binding affinity, and an electrophoretic mobility assay indicated a T cell specific reduction of protein binding for the G allele. Overexpression of GATA-3 in HEK293 cells resulted in allele-specific binding of GATA-3, indicating the identity of GATA-3 as the binding protein. The identified association of GLT6D1 with AgP implicates this locus as an important susceptibility factor, and GATA-3 as a potential signaling component in the pathophysiology of periodontitis.
Url:
DOI: 10.1093/hmg/ddp508
Affiliations:
Links toward previous steps (curation, corpus...)
- to stream Istex, to step Corpus: 006392
- to stream Istex, to step Curation: 006392
- to stream Istex, to step Checkpoint: 001A14
- to stream Main, to step Merge: 004F53
- to stream Main, to step Curation: 004F12
Le document en format XML
<record><TEI wicri:istexFullTextTei="biblStruct"><teiHeader><fileDesc><titleStmt><title>A genome-wide association study identifies GLT6D1 as a susceptibility locus for periodontitis</title><author><name sortKey="Schaefer, Arne S" sort="Schaefer, Arne S" uniqKey="Schaefer A" first="Arne S." last="Schaefer">Arne S. Schaefer</name></author><author><name sortKey="Richter, Gesa M" sort="Richter, Gesa M" uniqKey="Richter G" first="Gesa M." last="Richter">Gesa M. Richter</name></author><author><name sortKey="Nothnagel, Michael" sort="Nothnagel, Michael" uniqKey="Nothnagel M" first="Michael" last="Nothnagel">Michael Nothnagel</name></author><author><name sortKey="Manke, Thomas" sort="Manke, Thomas" uniqKey="Manke T" first="Thomas" last="Manke">Thomas Manke</name></author><author><name sortKey="Dommisch, Henrik" sort="Dommisch, Henrik" uniqKey="Dommisch H" first="Henrik" last="Dommisch">Henrik Dommisch</name></author><author><name sortKey="Jacobs, Gunnar" sort="Jacobs, Gunnar" uniqKey="Jacobs G" first="Gunnar" last="Jacobs">Gunnar Jacobs</name></author><author><name sortKey="Arlt, Alexander" sort="Arlt, Alexander" uniqKey="Arlt A" first="Alexander" last="Arlt">Alexander Arlt</name></author><author><name sortKey="Rosenstiel, Philip" sort="Rosenstiel, Philip" uniqKey="Rosenstiel P" first="Philip" last="Rosenstiel">Philip Rosenstiel</name></author><author><name sortKey="Noack, Barbara" sort="Noack, Barbara" uniqKey="Noack B" first="Barbara" last="Noack">Barbara Noack</name></author><author><name sortKey="Groessner Schreiber, Birte" sort="Groessner Schreiber, Birte" uniqKey="Groessner Schreiber B" first="Birte" last="Groessner-Schreiber">Birte Groessner-Schreiber</name></author><author><name sortKey="Jepsen, S Ren" sort="Jepsen, S Ren" uniqKey="Jepsen S" first="S Ren" last="Jepsen">S Ren Jepsen</name></author><author><name sortKey="Loos, Bruno G" sort="Loos, Bruno G" uniqKey="Loos B" first="Bruno G." last="Loos">Bruno G. Loos</name></author><author><name sortKey="Schreiber, Stefan" sort="Schreiber, Stefan" uniqKey="Schreiber S" first="Stefan" last="Schreiber">Stefan Schreiber</name></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:C8FBFA1B6F9E6A0D2E5944295AB23D42384440C8</idno><date when="2010" year="2010">2010</date><idno type="doi">10.1093/hmg/ddp508</idno><idno type="url">https://api.istex.fr/document/C8FBFA1B6F9E6A0D2E5944295AB23D42384440C8/fulltext/pdf</idno><idno type="wicri:Area/Istex/Corpus">006392</idno><idno type="wicri:explorRef" wicri:stream="Istex" wicri:step="Corpus" wicri:corpus="ISTEX">006392</idno><idno type="wicri:Area/Istex/Curation">006392</idno><idno type="wicri:Area/Istex/Checkpoint">001A14</idno><idno type="wicri:explorRef" wicri:stream="Istex" wicri:step="Checkpoint">001A14</idno><idno type="wicri:doubleKey">0964-6906:2010:Schaefer A:a:genome:wide</idno><idno type="wicri:Area/Main/Merge">004F53</idno><idno type="wicri:Area/Main/Curation">004F12</idno><idno type="wicri:Area/Main/Exploration">004F12</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a">A genome-wide association study identifies GLT6D1 as a susceptibility locus for periodontitis</title><author><name sortKey="Schaefer, Arne S" sort="Schaefer, Arne S" uniqKey="Schaefer A" first="Arne S." last="Schaefer">Arne S. Schaefer</name><affiliation></affiliation><affiliation wicri:level="1"><country wicri:rule="url">Allemagne</country></affiliation><affiliation><wicri:noCountry code="syntax">???</wicri:noCountry></affiliation><affiliation wicri:level="1"><country wicri:rule="url">Allemagne</country></affiliation></author><author><name sortKey="Richter, Gesa M" sort="Richter, Gesa M" uniqKey="Richter G" first="Gesa M." last="Richter">Gesa M. Richter</name><affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation></author><author><name sortKey="Nothnagel, Michael" sort="Nothnagel, Michael" uniqKey="Nothnagel M" first="Michael" last="Nothnagel">Michael Nothnagel</name><affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation></author><author><name sortKey="Manke, Thomas" sort="Manke, Thomas" uniqKey="Manke T" first="Thomas" last="Manke">Thomas Manke</name><affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation></author><author><name sortKey="Dommisch, Henrik" sort="Dommisch, Henrik" uniqKey="Dommisch H" first="Henrik" last="Dommisch">Henrik Dommisch</name><affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation></author><author><name sortKey="Jacobs, Gunnar" sort="Jacobs, Gunnar" uniqKey="Jacobs G" first="Gunnar" last="Jacobs">Gunnar Jacobs</name><affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation></author><author><name sortKey="Arlt, Alexander" sort="Arlt, Alexander" uniqKey="Arlt A" first="Alexander" last="Arlt">Alexander Arlt</name><affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation></author><author><name sortKey="Rosenstiel, Philip" sort="Rosenstiel, Philip" uniqKey="Rosenstiel P" first="Philip" last="Rosenstiel">Philip Rosenstiel</name><affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation></author><author><name sortKey="Noack, Barbara" sort="Noack, Barbara" uniqKey="Noack B" first="Barbara" last="Noack">Barbara Noack</name><affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation></author><author><name sortKey="Groessner Schreiber, Birte" sort="Groessner Schreiber, Birte" uniqKey="Groessner Schreiber B" first="Birte" last="Groessner-Schreiber">Birte Groessner-Schreiber</name><affiliation wicri:level="3"><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Operative Dentistry and Periodontology, University Medical Center Schleswig-Holstein, Campus Kiel, House 26, Arnold-Heller- Straße 3, Kiel 24105</wicri:regionArea><placeName><region type="land" nuts="2">Schleswig-Holstein</region><settlement type="city">Kiel</settlement></placeName></affiliation></author><author><name sortKey="Jepsen, S Ren" sort="Jepsen, S Ren" uniqKey="Jepsen S" first="S Ren" last="Jepsen">S Ren Jepsen</name><affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation></author><author><name sortKey="Loos, Bruno G" sort="Loos, Bruno G" uniqKey="Loos B" first="Bruno G." last="Loos">Bruno G. Loos</name><affiliation wicri:level="1"><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Periodontology, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and VU University Amsterdam, Louwesweg 1, Amsterdam 1066 EA</wicri:regionArea><wicri:noRegion>Amsterdam 1066 EA</wicri:noRegion></affiliation></author><author><name sortKey="Schreiber, Stefan" sort="Schreiber, Stefan" uniqKey="Schreiber S" first="Stefan" last="Schreiber">Stefan Schreiber</name><affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation></author></analytic><monogr></monogr><series><title level="j">Human Molecular Genetics</title><idno type="ISSN">0964-6906</idno><idno type="eISSN">1460-2083</idno><imprint><publisher>Oxford University Press</publisher><date type="published" when="2010-02-01">2010-02-01</date><biblScope unit="volume">19</biblScope><biblScope unit="issue">3</biblScope><biblScope unit="page" from="553">553</biblScope><biblScope unit="page" to="562">562</biblScope></imprint><idno type="ISSN">0964-6906</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0964-6906</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract">Periodontitis is a widespread, complex inflammatory disease of the mouth, which results in a loss of gingival tissue and alveolar bone, with aggressive periodontitis (AgP) as its most severe form. To identify genetic risk factors for periodontitis, we conducted a genome-wide association study in German AgP patients. We found AgP to be strongly associated with the intronic SNP rs1537415, which is located in the glycosyltransferase gene GLT6D1. We replicated the association in a panel of Dutch generalized and localized AgP patients. In the combined analysis including 1758 subjects, rs1537415 reached a genome-wide significance level of P= 5.51 × 10−9, OR = 1.59 (95% CI 1.36–1.86). The associated rare G allele of rs1537415 showed an enrichment of 10% in periodontitis cases (48.4% in comparison with 38.8% in controls). Fine-mapping and a haplotype analysis indicated that rs1537415 showed the strongest association signal. Sequencing identified no further associated variant. Tissue-specific expression analysis of GLT6D1 indicated high transcript levels in the leukocytes, the gingiva and testis. Analysis of potential transcription factor binding sites at this locus predicted a significant reduction of GATA-3 binding affinity, and an electrophoretic mobility assay indicated a T cell specific reduction of protein binding for the G allele. Overexpression of GATA-3 in HEK293 cells resulted in allele-specific binding of GATA-3, indicating the identity of GATA-3 as the binding protein. The identified association of GLT6D1 with AgP implicates this locus as an important susceptibility factor, and GATA-3 as a potential signaling component in the pathophysiology of periodontitis.</div></front></TEI><affiliations><list><country><li>Allemagne</li><li>Pays-Bas</li></country><region><li>Schleswig-Holstein</li></region><settlement><li>Kiel</li></settlement></list><tree><noCountry><name sortKey="Arlt, Alexander" sort="Arlt, Alexander" uniqKey="Arlt A" first="Alexander" last="Arlt">Alexander Arlt</name><name sortKey="Dommisch, Henrik" sort="Dommisch, Henrik" uniqKey="Dommisch H" first="Henrik" last="Dommisch">Henrik Dommisch</name><name sortKey="Jacobs, Gunnar" sort="Jacobs, Gunnar" uniqKey="Jacobs G" first="Gunnar" last="Jacobs">Gunnar Jacobs</name><name sortKey="Jepsen, S Ren" sort="Jepsen, S Ren" uniqKey="Jepsen S" first="S Ren" last="Jepsen">S Ren Jepsen</name><name sortKey="Manke, Thomas" sort="Manke, Thomas" uniqKey="Manke T" first="Thomas" last="Manke">Thomas Manke</name><name sortKey="Noack, Barbara" sort="Noack, Barbara" uniqKey="Noack B" first="Barbara" last="Noack">Barbara Noack</name><name sortKey="Nothnagel, Michael" sort="Nothnagel, Michael" uniqKey="Nothnagel M" first="Michael" last="Nothnagel">Michael Nothnagel</name><name sortKey="Richter, Gesa M" sort="Richter, Gesa M" uniqKey="Richter G" first="Gesa M." last="Richter">Gesa M. Richter</name><name sortKey="Rosenstiel, Philip" sort="Rosenstiel, Philip" uniqKey="Rosenstiel P" first="Philip" last="Rosenstiel">Philip Rosenstiel</name><name sortKey="Schreiber, Stefan" sort="Schreiber, Stefan" uniqKey="Schreiber S" first="Stefan" last="Schreiber">Stefan Schreiber</name></noCountry><country name="Allemagne"><noRegion><name sortKey="Schaefer, Arne S" sort="Schaefer, Arne S" uniqKey="Schaefer A" first="Arne S." last="Schaefer">Arne S. Schaefer</name></noRegion><name sortKey="Groessner Schreiber, Birte" sort="Groessner Schreiber, Birte" uniqKey="Groessner Schreiber B" first="Birte" last="Groessner-Schreiber">Birte Groessner-Schreiber</name><name sortKey="Schaefer, Arne S" sort="Schaefer, Arne S" uniqKey="Schaefer A" first="Arne S." last="Schaefer">Arne S. Schaefer</name></country><country name="Pays-Bas"><noRegion><name sortKey="Loos, Bruno G" sort="Loos, Bruno G" uniqKey="Loos B" first="Bruno G." last="Loos">Bruno G. Loos</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Santé/explor/EdenteV2/Data/Main/Exploration
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 004F12 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd -nk 004F12 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Wicri/Santé
|area= EdenteV2
|flux= Main
|étape= Exploration
|type= RBID
|clé= ISTEX:C8FBFA1B6F9E6A0D2E5944295AB23D42384440C8
|texte= A genome-wide association study identifies GLT6D1 as a susceptibility locus for periodontitis
}}
| This area was generated with Dilib version V0.6.32. |  |