Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Mar 17;10(1):4892.
doi: 10.1038/s41598-020-61819-0.

Translation of Mouse Model to Human Gives Insights Into Periodontitis Etiology

Affiliations
Free PMC article

Translation of Mouse Model to Human Gives Insights Into Periodontitis Etiology

Aysar Nashef et al. Sci Rep. .
Free PMC article

Abstract

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.

Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
Regional association plots of the most significant associations with AgP case-control cohort that located at the HLA loci, (A) HLA-DQH1 and (B) HLA-DPA1.
Figure 2
Figure 2
Regional association plots of the loci DAB2IP/TTLL11 and RNASE2, which suggested association in the meta-analyis of AgP and CP with p < 10−04. (A) DAB2IP/TTLL11. Left panel: The association upstream TTLL11, tagged by rs3763649, was observed in the discovery meta-analysis using AgP and CP cases and controls. Right panel: After exclusion of the CP case-control samples, the associated region was identical to the genetic locus associated with increased quantities of P.G. in humans (Red rectangle = region associated with increased quantities of P.G. in humans. (B) RNASE2. Left panel: The association of the suggested novel susceptibility locus of PD was strongest in the meta-analysis using AgP and CP cases and controls. Right panel: After exclusion of the CP case-control samples, the associated region was less significant, possibly reflecting the reduced statistical power.

Similar articles

See all similar articles

References

    1. Divaris K, et al. Genome-wide Association Study of Periodontal Pathogen Colonization. J. Dent. Res. 2012;91:S21–S28. doi: 10.1177/0022034512447951. - DOI - PMC - PubMed
    1. Divaris K, et al. Exploring the genetic basis of chronic periodontitis: A genome-wide association study. Hum. Mol. Genet. 2013;22:2312–2324. doi: 10.1093/hmg/ddt065. - DOI - PMC - PubMed
    1. Shimizu S, et al. A Genome-wide Association Study of Periodontitis in a Japanese Population. J. Dent. Res. 2015;94:555–561. doi: 10.1177/0022034515570315. - DOI - PubMed
    1. Teumer A, et al. Genome-wide association study of chronic periodontitis in a general German population. J. Clin. Periodontol. 2013;40:977–85. doi: 10.1111/jcpe.12154. - DOI - PubMed
    1. Hong, K.-W., Shin, M.-S., Ahn, Y.-B., Lee, H.-J. & Kim, H.-D. Genomewide association study on chronic periodontitis in Korean population: Results from the Yangpyeong health cohort. J. Clin. Periodontol. 42 (2015). - PubMed

LinkOut - more resources

Feedback