Relationship between inflammatory factors, white blood cells, and lumbar disc herniation

doi:10.12307/2026.756

Abstract

Abstract: BACKGROUND: Lumbar disc herniation is a clinically prevalent spinal disease. Existing evidence suggests that cytokines and white blood cells are closely associated with the occurrence and progression of lumbar disc herniation, but the specific mechanisms remain unclear.
OBJECTIVE: To explore the causal relationship between cytokines, white blood cells, and lumbar disc herniation using Mendelian randomization analysis.
METHODS: Using 91 cytokine datasets from the GWAS Catalog database and six types of white blood cell data from the Blood Cell Consortium as exposures, along with data on lumbar disc herniation from the latest R12 Finnish database as the outcome, bidirectional two-sample Mendelian randomization and genome-wide association study colocalization analyses were performed to investigate the causal relationships between cytokines, white blood cells, and lumbar disc herniation. Sensitivity tests, including the Steiger test, Cochran’s Q test, MR-Egger intercept assessment, and leave-one-out analysis, were conducted to verify the accuracy of the results. The inverse variance weighting method was primarily used for statistical analysis.
RESULTS AND CONCLUSION: (1) Basophils and eosinophils showed causal relationships with lumbar disc herniation (OR=0.93, 95%CI: 0.87–0.99; OR=0.94, 95%CI: 0.88–1.00). (2) Levels of S100 calcium-binding protein A12 (OR=0.74, 95%CI: 0.55–1.00), fibroblast growth factor (OR=1.03, 95%CI: 1.00–1.07), interleukin-20 receptor α protein (OR=1.09, 95%CI: 1.04–1.15), interleukin-6 (OR=1.07, 95%CI: 1.00–1.13), interleukin-7 (OR=1.08, 95%CI: 1.01–1.16), stem cell factor (OR=1.05, 95%CI: 1.01–1.09), and interleukin-2 (OR=0.94, 95%CI: 0.89–0.99) were causally associated with lumbar disc herniation. (3) In the colocalization analysis, the level of stem cell factor was found to be H3+H4=0.80, with the most significant single nucleotide polymorphism being rs6073966. These findings suggest that basophils, eosinophils, S100 calcium-binding protein A12, fibroblast growth factor, interleukin-20 receptor α protein, interleukin-2, interleukin-6, interleukin-7, and stem cell factor exhibit unidirectional causal effects on lumbar disc herniation. A potential related pathway may exist between stem cell factor and lumbar disc herniation.

Key words: cytokine, inflammation, bidirectional two-sample Mendelian randomization, colocalization, Steiger test, lumbar disc herniation

CLC Number:

Gu Shan, Zhang Long, Li Zhigang. Relationship between inflammatory factors, white blood cells, and lumbar disc herniation[J]. Chinese Journal of Tissue Engineering Research, 2026, 30(18): 4782-4790.

Figures/Tables 5

2.1 白细胞与腰椎间盘突出症的因果关系在剔除连锁不平衡和弱工具变量后，将6种白细胞分别作为暴露，腰椎间盘突出症作为结局，共筛选出188个与嗜碱性粒细胞相关的单核苷酸多态性、463个与白细胞相关的单核苷酸多态性、476个与单核细胞相关的单核苷酸多态性、471个与淋巴细胞相关的单核苷酸多态性、423个与嗜酸性粒细胞相关的单核苷酸多态性、395个与绝对中性粒细胞相关的单核苷酸多态性。孟德尔随机化结果表明循环系统中的嗜碱性粒细胞和嗜酸性粒细胞与腰椎间盘突出症具有因果关系(逆方差加权法：P=0.025，OR=0.93，95%CI：0.87-0.99；加权中位数法：P=0.042，OR=0.94，95%CI：0.88-1.00)，其余4种白细胞与腰椎间盘突出症风险均不具有显著因果关系(P > 0.05)(图2)。 2.2 细胞因子与腰椎间盘突出症的因果关系在剔除连锁不平衡和弱工具变量后，将91种细胞因子分别作为暴露，腰椎间盘突出症作为结局，共筛选出6种在遗传学上可能与腰椎间盘突出症存在关系的蛋白。其中，S100钙结合蛋白A12水平(逆方差加权法：P < 0.05，OR=1.08，95%CI：1.02- 1.13)、成纤维细胞生长因子水平(逆方差加权法：P < 0.05，OR=1.03，95%CI：1.00-1.07)、白细胞介素20受体α蛋白水平(逆方差加权法：P < 0.05，OR=1.09，95%CI：1.04-1.15)、白细胞介素6水平(逆方差加权法：P < 0.05，OR=1.07，95%CI：1.00-1.13)、白细胞介素7水平(逆方差加权法：P < 0.05，OR=1.08，95%CI：1.01-1.16)、干细胞因子水平(逆方差加权法：P < 0.05，OR=1.05，95%CI：1.01-1.09)与腰椎间盘突出症呈正相关因果关系，而白细胞介素2水平(逆方差加权法：P < 0.05，OR=0.94，95%CI：0.89-0.99)与腰椎间盘突出症呈负相关因果关系(图3-5)。该研究同时采用MR?Egger"

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