Department of Orthopedics, Fujian Medical University Union Hospital, Fuzhou, Fujian, China.
Department of Emergency, Zhaotong Traditional Chinese Medicine Hospital, Zhaotong, Yunnan, China.
Front Endocrinol (Lausanne). 2024 Sep 13;15:1370985. doi: 10.3389/fendo.2024.1370985. eCollection 2024.
Epidemiological and experimental evidence suggests that chronic inflammation plays an important role in the onset and progression of sarcopenia. However, there is inconsistent data on the inflammatory cytokines involved in the pathogenesis of sarcopenia. Therefore, we performed a two-sample Mendelian randomization (MR) analysis to explore the causal relationship between circulating cytokines and sarcopenia-related traits.
The MR analysis utilized genetic data from genome-wide association study that included genetic variations in 41 circulating cytokines and genetic variant data for appendicular lean mass (ALM), hand grip strength, and usual walking pace. Causal associations were primarily explored using the inverse variance-weighted (IVW) method, supplemented by MR-Egger, simple mode, weighted median, and weighted mode analyses. Additionally, sensitivity analyses were also performed to ensure the reliability and stability of the results.
Three cytokines [hepatocyte growth factor (HGF), interferon gamma-induced protein 10 (IP-10), and macrophage colony-stimulating factor (M-CSF)] were positively associated with ALM (β: 0.0221, 95% confidence interval (CI): 0.0071, 0.0372, = 0.0039 for HGF; β: 0.0096, 95%CI: 4e-04, 0.0189, = 0.0419 for IP-10; and β: 0.0100, 95%CI: 0.0035, 0.0165, = 0.0025 for M-CSF). Conversely, higher levels of interleukin-7 (IL-7), monocyte chemotactic protein 3 (MCP-3), and regulated on activation, normal T cell expressed and secreted (RANTES) were associated with decreased hand grip strength (β: -0.0071, 95%CI: -0.0127, -0.0014, = 0.0140 for IL-7; β: -0.0064, 95%CI: -0.0123, -6e-04, = 0.0313 for MCP-3; and β: -0.0082, 95%CI: -0.0164, -1e-04, = 0.0480 for RANTES). Similarly, interleukin 1 receptor antagonist (IL-1RA) was negatively correlated with usual walking pace (β: -0.0104, 95%CI: -0.0195, -0.0013, = 0.0254). Sensitivity analysis confirmed the robustness of these findings.
Our study provides additional insights into the pivotal role of specific inflammatory cytokines in the pathogenesis of sarcopenia. Further research is required to determine whether these cytokines can be used as targets for the prevention and treatment of sarcopenia.
流行病学和实验证据表明，慢性炎症在肌肉减少症的发病和进展中起着重要作用。然而，涉及肌肉减少症发病机制的炎症细胞因子的数据并不一致。因此，我们进行了两样本孟德尔随机化（MR）分析，以探讨循环细胞因子与与肌肉减少症相关特征之间的因果关系。
MR 分析利用了全基因组关联研究中的遗传数据，其中包括 41 种循环细胞因子的遗传变异和四肢瘦质量（ALM）、手握力和通常步行速度的遗传变异数据。主要使用逆方差加权（IVW）方法探索因果关系，补充了 MR-Egger、简单模式、加权中位数和加权模式分析。此外，还进行了敏感性分析以确保结果的可靠性和稳定性。
三种细胞因子[肝细胞生长因子（HGF）、干扰素γ诱导蛋白 10（IP-10）和巨噬细胞集落刺激因子（M-CSF）]与 ALM 呈正相关（β：0.0221，95%置信区间（CI）：0.0071，0.0372，=0.0039 用于 HGF；β：0.0096，95%CI：4e-04，0.0189，=0.0419 用于 IP-10；和 β：0.0100，95%CI：0.0035，0.0165，=0.0025 用于 M-CSF）。相反，较高水平的白细胞介素 7（IL-7）、单核细胞趋化蛋白 3（MCP-3）和调节激活正常 T 细胞表达和分泌（RANTES）与握力下降相关（β：-0.0071，95%CI：-0.0127，-0.0014，=0.0140 用于 IL-7；β：-0.0064，95%CI：-0.0123，-6e-04，=0.0313 用于 MCP-3；和 β：-0.0082，95%CI：-0.0164，-1e-04，=0.0480 用于 RANTES）。同样，白细胞介素 1 受体拮抗剂（IL-1RA）与通常的步行速度呈负相关（β：-0.0104，95%CI：-0.0195，-0.0013，=0.0254）。敏感性分析证实了这些发现的稳健性。
我们的研究提供了更多关于特定炎症细胞因子在肌肉减少症发病机制中的关键作用的信息。需要进一步研究以确定这些细胞因子是否可作为预防和治疗肌肉减少症的靶点。
