• World Neurosurg · Sep 2024

    Discovering Potential Mechanisms of Intervertebral Disc Disease Using Systematic Mendelian Randomization of Human Circulating Immunocytomics.

    • Ding-Qiang Chen, Zhi-Qiang Que, Wen-Bin Xu, Ke-Yi Xiao, Nai-Kun Sun, Jin-Yi Feng, Guang-Xun Lin, and Gang Rui.
    • Department of Orthopedics, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, China; The School of Clinical Medicine, Fujian Medical University, Fuzhou, China.
    • World Neurosurg. 2024 Sep 1; 189: e688e695e688-e695.

    BackgroundAlthough intervertebral disc degeneration (IVDD) is a critical factor in many spine-related diseases and has an extremely high prevalence in the aging population, the potential pathogenesis remains to be clarified entirely. Immune cells have been found to perform an essential function during the onset and progression of IVDD in recent years. Therefore, we explored the association between immune cell characteristics and IVDD through Mendelian randomization (MR) analysis and further delved into the mediating role of potential metabolites.MethodsBased on the MR analysis, the association of 731 immune cell phenotypes and 1400 metabolites on IVDD were assessed. Single nucleotide polymorphisms were closely associated the expression levels of immune cell characteristics and the concentrations of metabolites and have been used as instrumental variables for deducing them as risk factors or protective factors for IVDD. In addition, mediation analyses have been performed to identify potential metabolite mediators between immune cell characteristics and IVDD.ResultsMR analysis identified 27 immune cell phenotypes and 79 metabolites significantly associated with IVDD. In addition, mediation analysis was performed by selecting the immune cell phenotype that most significantly increased the risk of IVDD - CD86 on monocytes. A total of 4 metabolite-mediated mediation relationships were revealed (3 b-hydroxy-5-cholenoic acid, X-22509, N-acetyl-L-glutamine, and N2-acetyl, N6, N6-dimethyllysine).ConclusionsThe findings of this analysis identified underlying association between immune cell phenotypes, metabolite, and IVDD that may serve as predictive and prognostic clinical biomarkers and benefit IVDD pathogenesis research.Copyright © 2024 Elsevier Inc. All rights reserved.

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