Dataset Information

Gene Interaction Network Analysis Reveals IFI44L as a Drug Target in Rheumatoid Arthritis and Periodontitis.

ABSTRACT:

Objective

Despite extensive research on periodontitis and rheumatoid arthritis, the underlying molecular connectivity between these condition remains largely unknown. This research aimed to integrate periodontitis and rheumatoid arthritis gene expression profiles to identify interconnecting genes and focus to develop a common lead molecule against these inflammatory conditions.

Materials and methods

Differentially expressed genes (DEGs) of periodontitis and rheumatoid arthritis were identified from the datasets retrieved from the Gene Expression Omnibus database. The network was constructed by merging DEGs, and the interconnecting genes were identified and ranked using GeneMANIA. For the selected top ranked gene, the potential inhibitor was searched using FINDSITE^comb2.0. Subsequently, the molecular docking and molecular dynamics were performed to determine the binding efficiency and protein-ligand complex stability, respectively.

Results

From the network analysis, IFN-induced protein 44-like (IFI44L) was identified as a top ranked gene involved in most of the immunological pathway. With further virtual screening of 6507 molecules, vemurafenib was identified to be the best fit against the IFI44L target. The binding energy and stability of IFI44L with vemurafenib were investigated using molecular docking and molecular dynamics simulation. Docking results show binding energy of -7.7 Kcal/mol, and the simulation results show stability till 100 ns.

Conclusions

The identified IFI44L may represent a common drug target for periodontitis and rheumatoid arthritis. Vemurafenib could be a potent anti-inflammatory drug for both diseases.

SUBMITTER: Yadalam PK

PROVIDER: S-EPMC9104995 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

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Publications

Gene Interaction Network Analysis Reveals IFI44L as a Drug Target in Rheumatoid Arthritis and Periodontitis.

Yadalam Pradeep Kumar PK Sivasankari Thilagar T Rengaraj Santhiya S Mugri Maryam H MH Sayed Mohammed M Khan Samar Saeed SS Kamil Mona Awad MA Bhandi Shilpa S Raj A Thirumal AT Patil Shankargouda S Heboyan Artak A

Molecules (Basel, Switzerland) 20220425 9

<h4>Objective</h4>Despite extensive research on periodontitis and rheumatoid arthritis, the underlying molecular connectivity between these condition remains largely unknown. This research aimed to integrate periodontitis and rheumatoid arthritis gene expression profiles to identify interconnecting genes and focus to develop a common lead molecule against these inflammatory conditions.<h4>Materials and methods</h4>Differentially expressed genes (DEGs) of periodontitis and rheumatoid arthritis we ...[more]

PMID: 35566100

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Project description:ObjectiveTo examine the degree to which shared risk factors explain the relationship of periodontitis (PD) to rheumatoid arthritis (RA) and to determine the associations of PD and Porphyromonas gingivalis with pathologic and clinical features of RA.MethodsPatients with RA (n = 287) and patients with osteoarthritis as disease controls (n = 330) underwent a standardized periodontal examination. The HLA-DRB1 status of all participants was imputed using single-nucleotide polymorphisms from the extended major histocompatibility complex. Circulating anti-P gingivalis antibodies were measured using an enzyme-linked immunosorbent assay, and subgingival plaque was assessed for the presence of P gingivalis using polymerase chain reaction (PCR). Associations of PD with RA were examined using multivariable regression.ResultsPresence of PD was more common in patients with RA and patients with anti-citrullinated protein antibody (ACPA)-positive RA (n = 240; determined using the anti-cyclic citrullinated peptide 2 [anti-CCP-2] test) than in controls (35% and 37%, respectively, versus 26%; P = 0.022 and P = 0.006, respectively). There were no differences between RA patients and controls in the levels of anti-P gingivalis or the frequency of P gingivalis positivity by PCR. The anti-P gingivalis findings showed a weak, but statistically significant, association with the findings for both anti-CCP-2 (r = 0.14, P = 0.022) and rheumatoid factor (RF) (r = 0.19, P = 0.001). Presence of PD was associated with increased swollen joint counts (P = 0.004), greater disease activity according to the 28-joint Disease Activity Score using C-reactive protein level (P = 0.045), and higher total Sharp scores of radiographic damage (P = 0.015), as well as with the presence and levels of anti-CCP-2 (P = 0.011) and RF (P < 0.001). The expression levels of select ACPAs (including antibodies to citrullinated filaggrin) were higher in patients with subgingival P gingivalis and in those with higher levels of anti-P gingivalis antibodies, irrespective of smoking status. Associations of PD with established seropositive RA were independent of all covariates examined, including evidence of P gingivalis infection.ConclusionBoth PD and P gingivalis appear to shape the autoreactivity of RA. In addition, these results demonstrate an independent relationship between PD and established seropositive RA.

Dataset Information

Gene Interaction Network Analysis Reveals IFI44L as a Drug Target in Rheumatoid Arthritis and Periodontitis.

Objective

Materials and methods

Results

Conclusions

Publications

Gene Interaction Network Analysis Reveals IFI44L as a Drug Target in Rheumatoid Arthritis and Periodontitis.

Similar Datasets

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