dc.contributor.author
Müller, Ricarda
dc.contributor.author
Freitag‐Wolf, Sandra
dc.contributor.author
Weiner, January
dc.contributor.author
Chopra, Avneesh
dc.contributor.author
Top, Tugba
dc.contributor.author
Dommisch, Henrik
dc.contributor.author
Schaefer, Arne S.
dc.date.accessioned
2025-03-26T11:26:32Z
dc.date.available
2025-03-26T11:26:32Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/47039
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-46756
dc.description.abstract
Aim
The basis of phenotypic variation of periodontitis is genetic variability. Disease relevant effects of individual risk alleles are considered to result from genetic interactions. We investigated gene × gene (G×G) interactions of suggestive periodontitis susceptibility alleles.
Materials and Methods
We used the case-only design and investigated single-nucleotide polymorphism (SNPs) that showed associations in our recent genome-wide association study (GWAS) and GWAS meta-analysis with p < 5 × 10−6. CRISPR-dCas9 gene activation followed by RNA-sequencing and gene-set enrichment analyses elucidated differentially expressed genes and gene networks. With the databases of SNPInspector and Transfac professional, luciferase reporter gene assays and antibody electrophoretic mobility shift experiments, we analysed allele-specific effects on transcription factor binding.
Results
SNPs at the genes sialic acid binding Ig-like lectin 5 (SIGLEC5) and plasminogen (PLG) showed G×G interactions with rs1122900 at the long non-coding RNA (lncRNA) CTD-2353F22. Associated chromatin cis-activated CTD-2353F22.1 6.5-fold (p = .003), indicating CTD-2353F22.1 as target gene of this interaction. CTD-2353F22.1 regulated GADD45A (padj < 4.9 × 10−11, log2 fold change (FC) = −0.55), THBS1, SERPINE1 and Tissue Factor F3 (padj < 5 × 10−7, log2 FC ≥ −0.35) and the gene set “angiogenesis” (area under the curve = 0.71, padj = 8.2 × 10−5). rs1122900 effect C-allele decreased reporter gene activity (5.5-fold, p = .0003) and PRDM14 binding (76%).
Conclusions
CTD-2353F22.1 mediates interaction of SIGLEC5 and PLG, together with genes that function in periodontal wound healing.
en
dc.rights.uri
https://creativecommons.org/licenses/by-nc/4.0/
dc.subject
angiogenesis
en
dc.subject
case-only design
en
dc.subject
gene-gene interaction
en
dc.subject
periodontitis
en
dc.subject.ddc
600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::610 Medizin und Gesundheit
dc.title
Case-only design identifies interactions of genetic risk variants at SIGLEC5 and PLG with the lncRNA CTD-2353F22.1 implying the importance of periodontal wound healing for disease aetiology
dc.type
Wissenschaftlicher Artikel
dcterms.bibliographicCitation.doi
10.1111/jcpe.13712
dcterms.bibliographicCitation.journaltitle
Journal of Clinical Periodontology
dcterms.bibliographicCitation.number
1
dcterms.bibliographicCitation.originalpublishername
Wiley
dcterms.bibliographicCitation.pagestart
90
dcterms.bibliographicCitation.pageend
101
dcterms.bibliographicCitation.volume
50
refubium.affiliation
Charité - Universitätsmedizin Berlin
refubium.funding
DEAL Wiley
refubium.resourceType.isindependentpub
no
dcterms.accessRights.openaire
open access
dcterms.bibliographicCitation.pmid
36129033
dcterms.isPartOf.issn
0303-6979
dcterms.isPartOf.eissn
1600-051X