CDKN2BAS is associated with periodontitis in different European populations and is activated by bacterial infection
Identifieur interne : 004F08 ( Main/Exploration ); précédent : 004F07; suivant : 004F09CDKN2BAS is associated with periodontitis in different European populations and is activated by bacterial infection
Auteurs : Arne S. Schaefer [Allemagne] ; Gesa M. Richter [Allemagne] ; Henrik Dommisch [Allemagne] ; Markus Reinartz [Allemagne] ; Michael Nothnagel [Allemagne] ; Barbara Noack [Allemagne] ; Marja L. Laine [Pays-Bas] ; Mathias Folwaczny [Allemagne] ; Birte Groessner-Schreiber [Allemagne] ; Bruno G. Loos [Pays-Bas] ; S Ren Jepsen [Allemagne] ; Stefan Schreiber [Allemagne]Source :
- Journal of Medical Genetics [ 0022-2593 ] ; 2011-01.
Descripteurs français
- Wicri :
- topic : Consortium.
English descriptors
- KwdEn :
- Aggressive periodontitis, Allele, Anril, Association studies, Association study, Atherosclerotic plaque burden, Bacterial infection, Bacterial stimulation, Blank medium, Bonferroni correction, Broblasts, Causative, Causative variant, Cdk4, Cdkn2a, Cdkn2a mrna levels, Cdkn2b, Cdkn2bas, Cdkn2bas transcript levels, Center campus kiel, Chromosome, Chronic periodontitis, Connective tissue, Consortium, Coronary artery disease, Coronary heart disease, Covariate, Covariate adjustment, Different donors, Different european populations, Different populations, Epithelial, Epithelium, Gecs, Genet, Genetic, Genetic region, Genotype, German controls, Gingival, Gingival epithelium, Gingival tissue samples, Gingivalis, Gingivalis stimulation, Gordonii, Gordonii gecs, Gure, Hgfs, Human gingival, Kiel, Locus, Mrna, Mrna levels, Multiple comparisons, Pathogenic, Periodontal, Periodontitis, Polymorphism, Porphyromonas gingivalis, Rare allele, Recent study, Risk allele, Similar reduction, Single nucleotide polymorphisms, Snp, Statistical power, Streptococcus gordonii, Supplementary table, Tagsnps, Transcript, Transcript levels, Transcriptional, Unstimulated, Unstimulated gecs, Variant.
- Teeft :
- Aggressive periodontitis, Allele, Anril, Association studies, Association study, Atherosclerotic plaque burden, Bacterial infection, Bacterial stimulation, Blank medium, Bonferroni correction, Broblasts, Causative, Causative variant, Cdk4, Cdkn2a, Cdkn2a mrna levels, Cdkn2b, Cdkn2bas, Cdkn2bas transcript levels, Center campus kiel, Chromosome, Chronic periodontitis, Connective tissue, Consortium, Coronary artery disease, Coronary heart disease, Covariate, Covariate adjustment, Different donors, Different european populations, Different populations, Epithelial, Epithelium, Gecs, Genet, Genetic, Genetic region, Genotype, German controls, Gingival, Gingival epithelium, Gingival tissue samples, Gingivalis, Gingivalis stimulation, Gordonii, Gordonii gecs, Gure, Hgfs, Human gingival, Kiel, Locus, Mrna, Mrna levels, Multiple comparisons, Pathogenic, Periodontal, Periodontitis, Polymorphism, Porphyromonas gingivalis, Rare allele, Recent study, Risk allele, Similar reduction, Single nucleotide polymorphisms, Snp, Statistical power, Streptococcus gordonii, Supplementary table, Tagsnps, Transcript, Transcript levels, Transcriptional, Unstimulated, Unstimulated gecs, Variant.
Abstract
Epidemiological studies have indicated a relationship between coronary heart disease (CHD) and periodontitis. Recently, CDKN2BAS was reported as a shared genetic risk factor of CHD and aggressive periodontitis (AgP), but the causative variant has remained unknown. To identify and validate risk variants in different European populations, we first explored 150 kb of the genetic region of CDKN2BAS including the adjacent genes CDKN2A and CDKN2B, covering 51 tagging single nucleotide polymorphisms (tagSNPs) in AgP and chronic periodontitis (CP) in individuals of Dutch origin (n=313). In a second step, we tested the significant SNP associations in an independent AgP and CP population of German origin (n=1264). For the tagSNPs rs1360590, rs3217992, and rs518394, we could validate the associations with AgP before and after adjustment for the covariates smoking, gender and diabetes, with SNP rs3217992 being the most significant (OR 1.48, 95% CI 1.19 to 1.85; p=0.0004). We further showed in vivo gene expression of CDKN2BAS, CDKN2A, CDKN2B, and CDK4 in healthy and inflamed gingival epithelium (GE) and connective tissue (CT), and detected a significantly higher expression of CDKN2BAS in healthy CT compared to GE (p=0.004). After 24 h of stimulation with Porphyromonas gingivalis in Streptococcus gordonii pre-treated gingival fibroblast (HGF) and cultured gingival epithelial cells (GECs), we observed a 25-fold and fourfold increase of CDKN2BAS gene expression in HGFs (p=0.003) and GECs (p=0.004), respectively. Considering the global importance of CDKN2BAS in the disease risk of CHD, this observation supports the theory of inflammatory components in the disease physiology of CHD.
Url:
DOI: 10.1136/jmg.2010.078998
Affiliations:
- Allemagne, Pays-Bas
- Bavière, District de Cologne, District de Dresde, District de Haute-Bavière, Hollande-Septentrionale, Rhénanie-du-Nord-Westphalie, Saxe (Land), Schleswig-Holstein
- Amsterdam, Bonn, Dresde, Kiel, Munich
- Université Louis-et-Maximilien de Munich
Links toward previous steps (curation, corpus...)
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Le document en format XML
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Richter</name><affiliation wicri:level="3"><country xml:lang="fr">Allemagne</country><wicri:regionArea>Christian-Albrechts-University Kiel, Institute for Clinical Molecular Biology, Kiel</wicri:regionArea><placeName><region type="land" nuts="2">Schleswig-Holstein</region><settlement type="city">Kiel</settlement></placeName></affiliation></author><author><name sortKey="Dommisch, Henrik" sort="Dommisch, Henrik" uniqKey="Dommisch H" first="Henrik" last="Dommisch">Henrik Dommisch</name><affiliation wicri:level="3"><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Periodontology, Operative and Preventive Dentistry, University of Bonn, Bonn</wicri:regionArea><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Cologne</region><settlement type="city">Bonn</settlement></placeName></affiliation></author><author><name sortKey="Reinartz, Markus" sort="Reinartz, Markus" uniqKey="Reinartz M" first="Markus" last="Reinartz">Markus Reinartz</name><affiliation wicri:level="3"><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Periodontology, Operative and Preventive Dentistry, University of Bonn, Bonn</wicri:regionArea><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Cologne</region><settlement type="city">Bonn</settlement></placeName></affiliation></author><author><name sortKey="Nothnagel, Michael" sort="Nothnagel, Michael" uniqKey="Nothnagel M" first="Michael" last="Nothnagel">Michael Nothnagel</name><affiliation wicri:level="3"><country xml:lang="fr">Allemagne</country><wicri:regionArea>University Medical Center Schleswig-Holstein, Campus Kiel, Institute of Medical Informatics and Statistics, Kiel</wicri:regionArea><placeName><region type="land" nuts="2">Schleswig-Holstein</region><settlement type="city">Kiel</settlement></placeName></affiliation></author><author><name sortKey="Noack, Barbara" sort="Noack, Barbara" uniqKey="Noack B" first="Barbara" last="Noack">Barbara Noack</name><affiliation wicri:level="3"><country xml:lang="fr">Allemagne</country><wicri:regionArea>University Medical Center Carl Gustav Carus der Technischen Universität Dresden, Zentrum für Zahn-, Mund- und Kieferheilkunde, Poliklinik für Zahnerhaltung, Dresden</wicri:regionArea><placeName><region type="land" nuts="1">Saxe (Land)</region><region type="district" nuts="2">District de Dresde</region><settlement type="city">Dresde</settlement></placeName></affiliation></author><author><name sortKey="Laine, Marja L" sort="Laine, Marja L" uniqKey="Laine M" first="Marja L" last="Laine">Marja L. Laine</name><affiliation wicri:level="3"><country xml:lang="fr" wicri:curation="lc">Pays-Bas</country><wicri:regionArea>Department of Periodontology, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and VU University, Amsterdam</wicri:regionArea><placeName><settlement type="city">Amsterdam</settlement><region nuts="2" type="province">Hollande-Septentrionale</region></placeName></affiliation></author><author><name sortKey="Folwaczny, Mathias" sort="Folwaczny, Mathias" uniqKey="Folwaczny M" first="Mathias" last="Folwaczny">Mathias Folwaczny</name><affiliation wicri:level="4"><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Preventive Dentistry and Periodontology, University of Munich, Munich</wicri:regionArea><placeName><region type="land" nuts="1">Bavière</region><region type="district" nuts="2">District de Haute-Bavière</region><settlement type="city">Munich</settlement><settlement type="city">Munich</settlement></placeName><orgName type="university">Université Louis-et-Maximilien de Munich</orgName></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>University Medical Center Schleswig-Holstein, Campus Kiel, Department of Operative Dentistry and Periodontology, Kiel</wicri:regionArea><placeName><region type="land" nuts="2">Schleswig-Holstein</region><settlement type="city">Kiel</settlement></placeName></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="3"><country xml:lang="fr" wicri:curation="lc">Pays-Bas</country><wicri:regionArea>Department of Periodontology, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and VU University, Amsterdam</wicri:regionArea><placeName><settlement type="city">Amsterdam</settlement><region nuts="2" type="province">Hollande-Septentrionale</region></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:level="3"><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Periodontology, Operative and Preventive Dentistry, University of Bonn, Bonn</wicri:regionArea><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Cologne</region><settlement type="city">Bonn</settlement></placeName></affiliation></author><author><name sortKey="Schreiber, Stefan" sort="Schreiber, Stefan" uniqKey="Schreiber S" first="Stefan" last="Schreiber">Stefan Schreiber</name><affiliation wicri:level="3"><country xml:lang="fr">Allemagne</country><wicri:regionArea>Christian-Albrechts-University Kiel, Institute for Clinical Molecular Biology, Kiel</wicri:regionArea><placeName><region type="land" nuts="2">Schleswig-Holstein</region><settlement type="city">Kiel</settlement></placeName></affiliation></author></analytic><monogr></monogr><series><title level="j">Journal of Medical Genetics</title><title level="j" type="abbrev">J Med Genet</title><idno type="ISSN">0022-2593</idno><idno type="eISSN">1468-6244</idno><imprint><publisher>BMJ Publishing Group Ltd</publisher><date type="published" when="2011-01">2011-01</date><biblScope unit="volume">48</biblScope><biblScope unit="issue">1</biblScope><biblScope unit="page" from="38">38</biblScope></imprint><idno type="ISSN">0022-2593</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0022-2593</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Aggressive periodontitis</term><term>Allele</term><term>Anril</term><term>Association studies</term><term>Association study</term><term>Atherosclerotic plaque burden</term><term>Bacterial infection</term><term>Bacterial stimulation</term><term>Blank medium</term><term>Bonferroni correction</term><term>Broblasts</term><term>Causative</term><term>Causative variant</term><term>Cdk4</term><term>Cdkn2a</term><term>Cdkn2a mrna levels</term><term>Cdkn2b</term><term>Cdkn2bas</term><term>Cdkn2bas transcript levels</term><term>Center campus kiel</term><term>Chromosome</term><term>Chronic periodontitis</term><term>Connective tissue</term><term>Consortium</term><term>Coronary artery disease</term><term>Coronary heart disease</term><term>Covariate</term><term>Covariate adjustment</term><term>Different donors</term><term>Different european populations</term><term>Different populations</term><term>Epithelial</term><term>Epithelium</term><term>Gecs</term><term>Genet</term><term>Genetic</term><term>Genetic region</term><term>Genotype</term><term>German controls</term><term>Gingival</term><term>Gingival epithelium</term><term>Gingival tissue samples</term><term>Gingivalis</term><term>Gingivalis stimulation</term><term>Gordonii</term><term>Gordonii gecs</term><term>Gure</term><term>Hgfs</term><term>Human gingival</term><term>Kiel</term><term>Locus</term><term>Mrna</term><term>Mrna levels</term><term>Multiple comparisons</term><term>Pathogenic</term><term>Periodontal</term><term>Periodontitis</term><term>Polymorphism</term><term>Porphyromonas gingivalis</term><term>Rare allele</term><term>Recent study</term><term>Risk allele</term><term>Similar reduction</term><term>Single nucleotide polymorphisms</term><term>Snp</term><term>Statistical power</term><term>Streptococcus gordonii</term><term>Supplementary table</term><term>Tagsnps</term><term>Transcript</term><term>Transcript levels</term><term>Transcriptional</term><term>Unstimulated</term><term>Unstimulated gecs</term><term>Variant</term></keywords><keywords scheme="Teeft" xml:lang="en"><term>Aggressive periodontitis</term><term>Allele</term><term>Anril</term><term>Association studies</term><term>Association study</term><term>Atherosclerotic plaque burden</term><term>Bacterial infection</term><term>Bacterial stimulation</term><term>Blank medium</term><term>Bonferroni correction</term><term>Broblasts</term><term>Causative</term><term>Causative variant</term><term>Cdk4</term><term>Cdkn2a</term><term>Cdkn2a mrna levels</term><term>Cdkn2b</term><term>Cdkn2bas</term><term>Cdkn2bas transcript levels</term><term>Center campus kiel</term><term>Chromosome</term><term>Chronic periodontitis</term><term>Connective tissue</term><term>Consortium</term><term>Coronary artery disease</term><term>Coronary heart disease</term><term>Covariate</term><term>Covariate adjustment</term><term>Different donors</term><term>Different european populations</term><term>Different populations</term><term>Epithelial</term><term>Epithelium</term><term>Gecs</term><term>Genet</term><term>Genetic</term><term>Genetic region</term><term>Genotype</term><term>German controls</term><term>Gingival</term><term>Gingival epithelium</term><term>Gingival tissue samples</term><term>Gingivalis</term><term>Gingivalis stimulation</term><term>Gordonii</term><term>Gordonii gecs</term><term>Gure</term><term>Hgfs</term><term>Human gingival</term><term>Kiel</term><term>Locus</term><term>Mrna</term><term>Mrna levels</term><term>Multiple comparisons</term><term>Pathogenic</term><term>Periodontal</term><term>Periodontitis</term><term>Polymorphism</term><term>Porphyromonas gingivalis</term><term>Rare allele</term><term>Recent study</term><term>Risk allele</term><term>Similar reduction</term><term>Single nucleotide polymorphisms</term><term>Snp</term><term>Statistical power</term><term>Streptococcus gordonii</term><term>Supplementary table</term><term>Tagsnps</term><term>Transcript</term><term>Transcript levels</term><term>Transcriptional</term><term>Unstimulated</term><term>Unstimulated gecs</term><term>Variant</term></keywords><keywords scheme="Wicri" type="topic" xml:lang="fr"><term>Consortium</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract">Epidemiological studies have indicated a relationship between coronary heart disease (CHD) and periodontitis. Recently, CDKN2BAS was reported as a shared genetic risk factor of CHD and aggressive periodontitis (AgP), but the causative variant has remained unknown. To identify and validate risk variants in different European populations, we first explored 150 kb of the genetic region of CDKN2BAS including the adjacent genes CDKN2A and CDKN2B, covering 51 tagging single nucleotide polymorphisms (tagSNPs) in AgP and chronic periodontitis (CP) in individuals of Dutch origin (n=313). In a second step, we tested the significant SNP associations in an independent AgP and CP population of German origin (n=1264). For the tagSNPs rs1360590, rs3217992, and rs518394, we could validate the associations with AgP before and after adjustment for the covariates smoking, gender and diabetes, with SNP rs3217992 being the most significant (OR 1.48, 95% CI 1.19 to 1.85; p=0.0004). We further showed in vivo gene expression of CDKN2BAS, CDKN2A, CDKN2B, and CDK4 in healthy and inflamed gingival epithelium (GE) and connective tissue (CT), and detected a significantly higher expression of CDKN2BAS in healthy CT compared to GE (p=0.004). After 24 h of stimulation with Porphyromonas gingivalis in Streptococcus gordonii pre-treated gingival fibroblast (HGF) and cultured gingival epithelial cells (GECs), we observed a 25-fold and fourfold increase of CDKN2BAS gene expression in HGFs (p=0.003) and GECs (p=0.004), respectively. Considering the global importance of CDKN2BAS in the disease risk of CHD, this observation supports the theory of inflammatory components in the disease physiology of CHD.</div></front></TEI><affiliations><list><country><li>Allemagne</li><li>Pays-Bas</li></country><region><li>Bavière</li><li>District de Cologne</li><li>District de Dresde</li><li>District de Haute-Bavière</li><li>Hollande-Septentrionale</li><li>Rhénanie-du-Nord-Westphalie</li><li>Saxe (Land)</li><li>Schleswig-Holstein</li></region><settlement><li>Amsterdam</li><li>Bonn</li><li>Dresde</li><li>Kiel</li><li>Munich</li></settlement><orgName><li>Université Louis-et-Maximilien de Munich</li></orgName></list><tree><country name="Allemagne"><region name="Schleswig-Holstein"><name sortKey="Schaefer, Arne S" sort="Schaefer, Arne S" uniqKey="Schaefer A" first="Arne S" last="Schaefer">Arne S. Schaefer</name></region><name sortKey="Dommisch, Henrik" sort="Dommisch, Henrik" uniqKey="Dommisch H" first="Henrik" last="Dommisch">Henrik Dommisch</name><name sortKey="Folwaczny, Mathias" sort="Folwaczny, Mathias" uniqKey="Folwaczny M" first="Mathias" last="Folwaczny">Mathias Folwaczny</name><name sortKey="Groessner Schreiber, Birte" sort="Groessner Schreiber, Birte" uniqKey="Groessner Schreiber B" first="Birte" last="Groessner-Schreiber">Birte Groessner-Schreiber</name><name sortKey="Jepsen, S Ren" sort="Jepsen, S Ren" uniqKey="Jepsen S" first="S Ren" last="Jepsen">S Ren Jepsen</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="Reinartz, Markus" sort="Reinartz, Markus" uniqKey="Reinartz M" first="Markus" last="Reinartz">Markus Reinartz</name><name sortKey="Richter, Gesa M" sort="Richter, Gesa M" uniqKey="Richter G" first="Gesa M" last="Richter">Gesa M. Richter</name><name sortKey="Schaefer, Arne S" sort="Schaefer, Arne S" uniqKey="Schaefer A" first="Arne S" last="Schaefer">Arne S. Schaefer</name><name sortKey="Schreiber, Stefan" sort="Schreiber, Stefan" uniqKey="Schreiber S" first="Stefan" last="Schreiber">Stefan Schreiber</name></country><country name="Pays-Bas"><region name="Hollande-Septentrionale"><name sortKey="Laine, Marja L" sort="Laine, Marja L" uniqKey="Laine M" first="Marja L" last="Laine">Marja L. Laine</name></region><name sortKey="Loos, Bruno G" sort="Loos, Bruno G" uniqKey="Loos B" first="Bruno G" last="Loos">Bruno G. Loos</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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