TY - JOUR
T1 - Translation of mouse model to human gives insights into periodontitis etiology
AU - Nashef, Aysar
AU - Matthias, Munz
AU - Weiss, Ervin
AU - Loos, Bruno G.
AU - Jepsen, Søren
AU - van der Velde, Nathalie
AU - Uitterlinden, André G.
AU - Wellmann, Jürgen
AU - Berger, Klaus
AU - Hoffmann, Per
AU - Laudes, Matthias
AU - Lieb, Wolfgang
AU - Franke, Andre
AU - Dommisch, Henrik
AU - Schäfer, Arne
AU - Houri-Haddad, Yael
AU - Iraqi, Fuad A.
N1 - Publisher Copyright:
© 2020, The Author(s).
PY - 2020/12/1
Y1 - 2020/12/1
N2 - To suggest candidate genes involved in periodontitis, we combined gene expression data of periodontal biopsies from Collaborative Cross (CC) mouse lines, with previous reported quantitative trait loci (QTL) in mouse and with human genome-wide association studies (GWAS) associated with periodontitis. Periodontal samples from two susceptible, two resistant and two lines that showed bone formation after periodontal infection were collected during infection and naïve status. Differential expressed genes (DEGs) were analyzed in a case-control and case-only design. After infection, eleven protein-coding genes were significantly stronger expressed in resistant CC lines compared to susceptible ones. Of these, the most upregulated genes were MMP20 (P = 0.001), RSPO4 (P = 0.032), CALB1 (P = 1.06×10−4), and AMTN (P = 0.05). In addition, human orthologous of candidate genes were tested for their association in a case-controls samples of aggressive (AgP) and chronic (CP) periodontitis (5,095 cases, 9,908 controls). In this analysis, variants at two loci, TTLL11/PTGS1 (rs9695213, P = 5.77×10−5) and RNASE2 (rs2771342, P = 2.84×10−5) suggested association with both AgP and CP. In the association analysis with AgP only, the most significant associations were located at the HLA loci HLA-DQH1 (rs9271850, P = 2.52×10−14) and HLA-DPA1 (rs17214512, P = 5.14×10−5). This study demonstrates the utility of the CC RIL populations as a suitable model to investigate the mechanism of periodontal disease.
AB - To suggest candidate genes involved in periodontitis, we combined gene expression data of periodontal biopsies from Collaborative Cross (CC) mouse lines, with previous reported quantitative trait loci (QTL) in mouse and with human genome-wide association studies (GWAS) associated with periodontitis. Periodontal samples from two susceptible, two resistant and two lines that showed bone formation after periodontal infection were collected during infection and naïve status. Differential expressed genes (DEGs) were analyzed in a case-control and case-only design. After infection, eleven protein-coding genes were significantly stronger expressed in resistant CC lines compared to susceptible ones. Of these, the most upregulated genes were MMP20 (P = 0.001), RSPO4 (P = 0.032), CALB1 (P = 1.06×10−4), and AMTN (P = 0.05). In addition, human orthologous of candidate genes were tested for their association in a case-controls samples of aggressive (AgP) and chronic (CP) periodontitis (5,095 cases, 9,908 controls). In this analysis, variants at two loci, TTLL11/PTGS1 (rs9695213, P = 5.77×10−5) and RNASE2 (rs2771342, P = 2.84×10−5) suggested association with both AgP and CP. In the association analysis with AgP only, the most significant associations were located at the HLA loci HLA-DQH1 (rs9271850, P = 2.52×10−14) and HLA-DPA1 (rs17214512, P = 5.14×10−5). This study demonstrates the utility of the CC RIL populations as a suitable model to investigate the mechanism of periodontal disease.
UR - http://www.scopus.com/inward/record.url?scp=85082014334&partnerID=8YFLogxK
U2 - 10.1038/s41598-020-61819-0
DO - 10.1038/s41598-020-61819-0
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C2 - 32184465
AN - SCOPUS:85082014334
SN - 2045-2322
VL - 10
JO - Scientific Reports
JF - Scientific Reports
IS - 1
M1 - 4892
ER -