Transcriptional Regulatory Signatures of Systemic Diseases in Periodontitis with Dyslipidemia

Background: Periodontitis is a chronic bacterial infection of tooth that increases the risk of systemic dis-eases like diabetes, cancer, and cardiovascular diseases. Although it has been have found altered lipids in periodontitis patients, its gene regulation is largely unknown. This study aimed to examine the lipid med-itated regulatory network in periodontitis that may helpful in early detection of periodontal mediated systemic diseases.Methods: We employed a high-throughput gene expression data of 1) patients with periodontitis (n = 6); 2) the periodontitis patients with dyslipidemia (n = 6); and 3) healthy control group (n = 6). The over rep-resented (DEGs) genes in SET-A (control vs. periodontitis) and SET-B (control vs. periodontitis with dys-lipidemia) was identified. The protein interaction network was generated for the over represented genes in both the conditions. The constructed network was dissected into multiple regulatory clusters, contain-ing over expressed transcription factors with its interacting proteins. Further the behavior of the clusters was determined through gene ontology and molecular pathways.Results: On expression analysis, 751 in SET-A and 561 in SET-B were over expressed compared to healthy control. Using over expressed genes, protein interaction networks were constructed for SET-A and SET-B, respectively. Topological analysis revel the difference in the complexity of both the network. Four regu-latory clusters (ESR1, FOS, RUNX2, and SP1) from SET-A and six (ESR1, ESR2, FOS, JDP2, PBX1, and TAL1) from the SET-B network was extracted. Each cluster displayed a variety of molecular mechanism associ-ated with immune system, cell cycle, and signal processing. Clusters from SET-B showed diverse regula-tory pattern in associated with cancer, neurological, psychiatric and metabolic diseases.Conclusion: Our findings demonstrate difference in regulatory patterns between periodontitis and peri-odontitis with dyslipidemia. These finding may provide evidence for dyslipidemia mediated periodontitis contribute to progressive systemic diseases. Further experiments are required to validate these regulators as biomarkers and drug targets.& COPY; 2023 The Author(s). Published by Elsevier B.V. on behalf of King Saud University. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).