Identification of Neuropeptides as Potential Crosstalks Linking Down Syndrome and Periodontitis Revealed by Transcriptomic Analyses

Abstract

Background. This bioinformatics study was aimed to investigate the relationship between periodontitis (PD) and Down Syndrome (DS) regarding potential crosstalk genes, related neuropeptides, and biological processes. Methods. Data for PD (GSE23586, GSE10334 and GSE16134) and DS (GSE35665) were downloaded from NCBI Gene Expression Omnibus (GEO). Following normalization and merging of PD data, differential expression analysis was performed ( p value < 0.05 and ∣ log FC ∣ ≥ 0.5 ). The common deregulated genes between PD and DS were considered as crosstalk genes. The significantly differentially expressed genes were used to construct the coexpression network and to further identify coexpression gene modules. To acquire the significant modules, the significant expression level of genes in the module was used to analyze the enrichment of genes in each module. Neuropeptides were assessed from NeuroPedia database. Neuropeptide genes and crosstalk genes were merged and mapped into PPI network, and the correlation coefficient (Spearman) was determined for the crosstalk genes. Results. 138 crosstalk genes were predicted. According to the functional enrichment analysis, these genes significantly regulated different biological processes and pathways. In enrichment analysis, the significant module of DS was pink module, and turquoise module was significant in PD. Four common crosstalk genes were acquired, i.e., CD19, FCRL5, FCRLA, and HLA-DOB. In the complex network, INS and IGF2 interacted with CASP3 and TP53, which commonly regulated the MAPK signaling pathway. Moreover, the results showed that TP53 interacted with IGF2 and INS inducing the dysregulation of PI3K-Akt signaling pathway. UBL was positively correlated with crosstalk genes in both diseases. LEP was revealed to be both a neuropeptide and crosstalk gene and was positively correlated with other crosstalk genes. Conclusion. Different crosstalk genes, related neuropeptides, and biological pathways and processes were revealed between PD and DS, which can serve as a theoretical basis for future research.

Discovering genetic linkage between periodontitis and type 1 diabetes: A bioinformatics study

“…For PD, a bioinformatics study indicated that IGF2 was intersected between PD and Major depressive disorder (Sun et al, 2021). Another study also predicted that IGF2 was involved in genetic crosstalk between PD and Down Syndrome, indicating the importance of IGF2 in the pathogenesis of PD (Chen et al, 2021). IGF2 could suppress the proliferation and osteogenic differentiation of periodontal ligament cells (Konermann et al, 2013).…”

Unveiling the m6A Methylation Regulator Links between Prostate Cancer and Periodontitis by Transcriptomic Analysis

“…Identifying the genetic links between two related diseases is possible because of the advent of computational biology and the analytical approach. Several bioinformatics studies have attempted to identify the crosstalk genes that are deregulated in PC and PD [12][13][14][15][16][17]. The present research similarly aims to identify the m6A RNA methylation regulators linking PC and PD.…”

Association of Down syndrome with periodontal diseases: Systematic review and meta‐analysis

“…Some researchers suggest that immunological abnormalities detected in DS individuals such as T cell development, decreased specific antibody response to immunizations, and neuthrophil chemotaxis defects, make them more susceptible to infections including periodontitis 7,8 . Therefore, it has been implied that periodontal disease is more frequent and severe in DS individuals 9,10 . While there is a suggested link between these two conditions, individual study results have yielded inconclusive findings.…”

“…7,8 Therefore, it has been implied that periodontal disease is more frequent and severe in DS individuals. 9,10 While there is a suggested link between these two conditions, individual study results have yielded inconclusive findings. Two studies, for example, found that the periodontal index and prevalence of periodontitis were not significantly different between DS and non-syndromic patients, despite a tendency for increased gingival inflammation severity in DS subjects.…”