Mardan Muradil, Mamat Mardan, Yasin Parhat, Cai Xiaoyu, Zheng Huoliang, Xu Qingyin, Song Shaokuan, Li Bo, Cai Hao, Chen Pengbo, Lu Zeyu, Omar Shahna, Jiang Shengdan, Jiang Leisheng, Zheng Xin-Feng
Department of Spine Center Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine Shanghai China.
Department of Spine Surgery The First Affiliated Hospital of Xinjiang Medical University Urumqi China.
JOR Spine. 2024 Dec 11;7(4):e70019. doi: 10.1002/jsp2.70019. eCollection 2024 Dec.
Scoliosis, characterized by a lateral curvature of the spine, affects millions globally. The role of inflammatory cytokines in the pathogenesis of scoliosis is increasingly acknowledged, yet their causal relationships remain poorly defined.
This study aims to explore the genetic-level causal relationships between inflammatory cytokines and scoliosis utilizing bidirectional Mendelian randomization (MR) analysis.
This study leverages genetic data from public Genome-Wide Association Studies (GWAS). Bidirectional MR was employed to investigate the causal relationships between 44 inflammatory cytokines and scoliosis. The inflammatory cytokine data include 8293 Finnish individuals, while the scoliosis data consist of 165 850 participants of European descent, including 1168 scoliosis cases and 164 682 controls. Causal links were assessed using the inverse variance-weighted method, supplemented by MR-Egger, weighted median, and weighted mode analyses. Heterogeneity and pleiotropy were assessed using standard tests, with sensitivity analysis conducted through leave-one-out analysis.
Our analysis demonstrated a significant causal association between the cytokine Resistin (RETN) and the development of scoliosis ( = 0.024, OR 95% CI = 1.344 [1.039-1.739]). No other cytokines among the 44 studied showed significant associations.
The findings highlight the critical role of RETN in scoliosis progression and underscore the complex interplay of genetic and inflammatory pathways. Further research is needed to explore additional biomarkers and their mechanisms in scoliosis.
This study provides evidence of a significant causal relationship between RETN and scoliosis, emphasizing its potential as a therapeutic target. These findings contribute to understanding scoliosis pathogenesis and pave the way for future research on inflammation-related pathways and therapies.
脊柱侧弯以脊柱侧曲为特征，全球数百万人受其影响。炎症细胞因子在脊柱侧弯发病机制中的作用日益受到认可，但其因果关系仍不明确。
本研究旨在利用双向孟德尔随机化（MR）分析探索炎症细胞因子与脊柱侧弯之间的基因水平因果关系。
本研究利用公开的全基因组关联研究（GWAS）的基因数据。采用双向MR研究44种炎症细胞因子与脊柱侧弯之间的因果关系。炎症细胞因子数据包括8293名芬兰人，而脊柱侧弯数据由165850名欧洲血统参与者组成，其中包括1168例脊柱侧弯病例和164682名对照。使用逆方差加权法评估因果联系，并辅以MR-Egger、加权中位数和加权模式分析。使用标准测试评估异质性和多效性，并通过留一法分析进行敏感性分析。
我们的分析表明，细胞因子抵抗素（RETN）与脊柱侧弯的发生之间存在显著因果关联（=0.024，OR 95%CI=1.344[1.039-1.739]）。在所研究的44种细胞因子中，没有其他细胞因子显示出显著关联。
研究结果突出了RETN在脊柱侧弯进展中的关键作用，并强调了遗传和炎症途径之间复杂的相互作用。需要进一步研究以探索脊柱侧弯中的其他生物标志物及其机制。
本研究提供了RETN与脊柱侧弯之间存在显著因果关系的证据，强调了其作为治疗靶点的潜力。这些发现有助于理解脊柱侧弯的发病机制，并为未来关于炎症相关途径和治疗的研究铺平道路。
