Han Zhaopu, Chen Yicheng, Ye Xiaojian
Department of Orthopedics, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200336, China.
Heliyon. 2024 Aug 28;10(17):e37044. doi: 10.1016/j.heliyon.2024.e37044. eCollection 2024 Sep 15.
There is still a lack of high-level evidence regarding the causal relationship between smoking and intervertebral disc degenerative diseases. This study utilized data from genome wide analysis studies and conducted two-sample Mendelian randomization analyses across multiple heterogeneous datasets. We evaluated the causal relationships between smoking behavior, serum inflammatory factors, serum chemokines, and intervertebral disc degeneration. Sensitivity analysis was performed to examine data heterogeneity and the pleiotropy of causal effects. The results indicated that smokers were liable to develop intervertebral disc degeneration (OR 1.770; 95 % CI, 1.519-2.064; p = 2.992 × 10-13), and long-term smoking behavior increased the risk of intervertebral disc degeneration (OR 1.715; 95 % CI 1.475-1.994; P = 2.220 × 10-12). Additionally, a causal relationship was confirmed between serum IL-1β level and intervertebral disc degeneration (OR 1.087; 95 % CI, 1.023-1.154; p = 0.007). The "smoking index" representing lifelong smoking habit was also found to be causally related to serum MCP-3 level(β = 0.292; SE = 0.093; p = 0.002). All of the causality mentioned above remained stable in sensitivity tests. Based on the analysis results and fundamental medicine theories around macrophage-induced inflammation in degenerative intervertebral discs, we have constructed a new mechanism that long-term smoking could induce an increase in serum MCP-3 level, promoting the gathering and activation of monocyte macrophages. Furthermore, the recruited macrophages led to an increase in local IL-1β within the intervertebral disc, ultimately exacerbating the process of intervertebral disc degeneration. What we have found is expected to accelerate the development of prevention and treatment of intervertebral disc degeneration.
关于吸烟与椎间盘退行性疾病之间的因果关系，目前仍缺乏高水平证据。本研究利用全基因组分析研究的数据，在多个异质数据集中进行了两样本孟德尔随机化分析。我们评估了吸烟行为、血清炎症因子、血清趋化因子与椎间盘退变之间的因果关系。进行了敏感性分析以检验数据异质性和因果效应的多效性。结果表明，吸烟者易患椎间盘退变（比值比1.770；95%可信区间，1.519 - 2.064；p = 2.992×10⁻¹³），长期吸烟行为增加了椎间盘退变的风险（比值比1.715；95%可信区间1.475 - 1.994；P = 2.220×10⁻¹²）。此外，证实血清白细胞介素-1β水平与椎间盘退变之间存在因果关系（比值比1.087；95%可信区间，1.023 - 1.154；p = 0.007）。还发现代表终生吸烟习惯的“吸烟指数”与血清单核细胞趋化蛋白-3水平存在因果关系（β = 0.292；标准误 = 0.093；p = 0.002）。上述所有因果关系在敏感性检验中均保持稳定。基于分析结果以及围绕巨噬细胞诱导退变椎间盘中炎症的基础医学理论，我们构建了一种新机制，即长期吸烟可导致血清单核细胞趋化蛋白-3水平升高，促进单核巨噬细胞的聚集和激活。此外，募集的巨噬细胞导致椎间盘中局部白细胞介素-1β增加，最终加剧椎间盘退变过程。我们的发现有望加速椎间盘退变防治的发展。
