Association between circulating inflammatory proteins and temporomandibular disorders

insight from a two-sample Mendelian randomization analysis

Authors

  • Ao Ding University of Science and Technology of China, The First Affiliated Hospital of USTC (Anhui Provincial Hospital), Department of Stomatology, Hefei, China.
  • Chan-Yuan Yu University of Science and Technology of China, The First Affiliated Hospital of USTC (Anhui Provincial Hospital), Department of Stomatology, Hefei, China.
  • Feng Jiang Obstetrics and Gynecology Hospital of Fudan University, Department of Neonatology, Shanghai, China. https://orcid.org/0000-0002-3525-8752
  • Chu-Yan Wu The First Affiliated Hospital of Nanjing Medical University, Department of Rehabilitation Medicine, Nanjing, China. https://orcid.org/0000-0002-5622-6020
  • Jun Zhao Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Ninth People’s Hospital, Department of Orthodontics, Shanghai, China. https://orcid.org/0000-0002-3067-9080

DOI:

https://doi.org/10.1590/1678-7757-2024-0112

Keywords:

Mendelian randomization, Circulating inflammatory proteins, Temporomandibular disorders, Genome-wide association studies

Abstract

Background  Past studies have indicated links between specific inflammatory proteins in the bloodstream and temporomandibular disorders (TMDs). Nonetheless, there remains the need for further solid research pinpointing the exact causes behind these associations. This Mendelian randomization (MR) study aims to examine the association between 91 circulating inflammatory proteins and TMDs.

Methodology  The most comprehensive genome-wide association studies available for circulating inflammatory proteins and TMDs was used in this two-sample MR analysis. The association between genetic predispositions to TMDs and levels of circulating inflammatory proteins was explored by various methods, including inverse variance weighted, MR-Egger, weighted median, simple mode, weighted mode, and MR-PRESSO techniques. To evaluate the reliability of these findings, sensitivity analyses such as Cochran’s Q test, the MR-Egger intercept test, and a leave-one-out approach were conducted.

Results  Findings indicated significant links between lower levels of circulating CCL4 (odds ratio, OR: 0.9241, 95% confidence interval, CI: 0.8679-0.984, p=0.0138), IL-20 (OR: 0.8615, 95%CI: 0.7566-0.9808, p=0.0243), and TWEAK (OR: 0.8702, 95%CI: 0.7634-0.992, p=0.0375) and an increased risk of TMDs, according to the inverse variance weighted method. Conversely, a higher level of S100A12 in the blood stream was associated with an increased risk of TMDs (OR: 1.1368, 95%CI: 1.0134-1.2752, p=0.0286). Sensitivity analyses confirmed the stability of these outcomes.

Conclusion  This study suggests that reduced levels of CCL4, IL-20, and TWEAK are associated with a higher risk of TMDs, alongside an increased risk of TMDs connected to elevated levels of S100A12.

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Published

2025-01-10 — Updated on 2025-01-14

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Vol. 32 (2024)

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Original Articles

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How to Cite

Ding, A., Yu, C.-Y., Jiang, F., Wu, C.-Y., & Zhao, J. (2025). Association between circulating inflammatory proteins and temporomandibular disorders: insight from a two-sample Mendelian randomization analysis. Journal of Applied Oral Science, 32, e20240112. https://doi.org/10.1590/1678-7757-2024-0112 (Original work published 2025)