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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Mucosal Immunity
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1440753
This article is part of the Research Topic The Causal Association and Mechanism between Oral Inflammatory Diseases and Systemic Diseases View all articles

Causal relationship, shared genes between rheumatoid arthritis and pulp and periapical disease: evidence from GWAS and transcriptome data

Provisionally accepted
Chenjie Qiu Chenjie Qiu 1*Huili Wu Huili Wu 2Lijuan Wang Lijuan Wang 2
  • 1 Changzhou Traditional Chinese Medicine Hospital, Changzhou, China
  • 2 Changzhou Stomatological Hospital, Changzhou, China

The final, formatted version of the article will be published soon.

    Objective: Patients with rheumatoid arthritis (RA) have an increased risk of developing pulp and periapical disease (PAP), but the causal relationship and shared genetic factors between these conditions have not been explored. This study aimed to investigate the bidirectional causal relationship between RA and PAP and to analyze shared genes and pathogenic pathways.We utilized GWAS data from the IEU Open GWAS Project and employed five Mendelian randomization methods (MR Egger, weighted median, inverse variance weighted, simple mode, and weighted mode) to investigate the bidirectional causal relationship between RA and PAP.Transcriptome data for RA and irreversible pulpitis (IRP) were obtained from the GEO database.Hub genes were identified through differential analysis, CytoHubba, machine learning (ML), and other methods. The immune infiltration of both diseases was analyzed using the ssGSEA method.Finally, we constructed a regulatory network for miRNAs, transcription factors, chemicals, diseases, and RNA-binding proteins based on the identified hub genes.Results: RA was significantly associated with an increased risk of PAP (OR = 1.1284, 95% CI 1.0674-1.1929, p < 0.001). However, there was insufficient evidence to support the hypothesis that PAP increased the risk of RA. Integrating datasets and differential analysis identified 84 shared genes primarily involved in immune and inflammatory pathways, including the IL-17 signaling pathway, Th17 cell differentiation, and TNF signaling pathway. Using CytoHubba and three ML methods, we identified three hub genes (HLA-DRA, ITGAX, and PTPRC) that are significantly correlated and valuable for diagnosing RA and IRP. We then constructed a comprehensive regulatory network using the miRDB, miRWalk, ChipBase, hTFtarget, CTD, MalaCards, DisGeNET, and ENCORI databases.RA may increase the risk of PAP. The three key genes, HLA-DRA, ITGAX, and PTPRC, have significant diagnostic value for both RA and IRP.

    Keywords: Rheumatoid arthritis, Pulp and periapical disease, Irreversible pulpitis, Mendelian randomization, Hub genes

    Received: 30 May 2024; Accepted: 27 Aug 2024.

    Copyright: © 2024 Qiu, Wu and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Chenjie Qiu, Changzhou Traditional Chinese Medicine Hospital, Changzhou, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.