School of Nursing, North Sichuan Medical College, Nanchong, China.
Department of Orthopaedics, Nanchong Central Hospital, The Second Clinical Institute of North Sichuan Medical College, Nanchong, China.
Cytokine. 2024 Dec;184:156777. doi: 10.1016/j.cyto.2024.156777. Epub 2024 Oct 11.
Carpal tunnel syndrome (CTS) and certain inflammatory cytokines have been linked in observational studies; however, the exact causative linkages remain unknown. The purpose of this study is to investigate any possible link between the onset of CTS and 91 inflammatory cytokines.
A two-sample bidirectional Mendelian randomization (MR) approach was used in this investigation. 91 circulating inflammatory cytokines' genetic variants were retrieved from the European ancestry genome-wide association study (GWAS) database. From germline GWAS, summary data for 24,766 CTS patients and 360,538 controls were gathered. The instrumental variables were single nucleotide polymorphisms (SNPs) that were highly correlated with the 91 inflammatory cytokines. The random-effects inverse-variance weighted (IVW) approach was employed in the primary analysis, and multiple comparisons were subjected to the Bonferroni correction. Sensitivity analysis was performed to evaluate the validity of the causal relationship.
Our findings showed a negative correlation between CCL19, FGF-19, IL-5, TGF-alpha, TRAIL, and the risk of CTS. Specifically, CCL19 (odds ratio [OR]: 0.944, 95 % confidence interval [CI]: 0.894-0.996, p = 0.0349), FGF-19 (OR: 0.940, 95 % CI: 0.894-0.987, p = 0.0133), IL-5 (OR: 0.936, 95 % CI: 0.885-0.990, p = 0.0212), TGF-alpha (OR: 0.902, 95 % CI: 0.838-0.970, p = 0.0057), and TRAIL (OR: 0.926, 95 % CI: 0.881-0.974, p = 0.0026) were inversely related to CTS risk. Conversely, CCL20, IL-2RB, and IL-6 were positively associated with an increased risk of CTS. Specifically, CCL20 (OR: 1.072, 95 % CI: 1.005-1.142, p = 0.0334), IL-2RB (OR: 1.067, 95 % CI: 1.001-1.137, p = 0.0463), and IL-6 (OR: 1.088, 95 % CI: 1.005-1.177, p = 0.0365) were positively correlated with CTS risk. Reverse Mendelian randomization analyses indicated no evidence of a reverse causal relationship between CTS and inflammatory cytokines.
According to this study, there is a causal link between CTS and certain inflammatory cytokines, which suggests that these cytokines may be important in the pathophysiology of CTS. To confirm these results and investigate the specific function of these cytokines in the beginning and development of CTS, more investigation is necessary.
腕管综合征（CTS）和某些炎症细胞因子在观察性研究中存在关联；然而，确切的因果联系仍不清楚。本研究旨在探讨 CTS 发病与 91 种炎症细胞因子之间是否存在任何关联。
本研究采用两样本双向孟德尔随机化（MR）方法。从欧洲血统全基因组关联研究（GWAS）数据库中获取了 91 种循环炎症细胞因子的遗传变异。从种系 GWAS 中，收集了 24766 例 CTS 患者和 360538 例对照的汇总数据。工具变量是与 91 种炎症细胞因子高度相关的单核苷酸多态性（SNP）。主要分析采用随机效应逆方差加权（IVW）方法，多重比较采用 Bonferroni 校正。进行敏感性分析以评估因果关系的有效性。
我们的研究结果表明，CCL19、FGF-19、IL-5、TGF-α、TRAIL 与 CTS 风险呈负相关。具体而言，CCL19（比值比[OR]：0.944，95%置信区间[CI]：0.894-0.996，p=0.0349）、FGF-19（OR：0.940，95%CI：0.894-0.987，p=0.0133）、IL-5（OR：0.936，95%CI：0.885-0.990，p=0.0212）、TGF-α（OR：0.902，95%CI：0.838-0.970，p=0.0057）和 TRAIL（OR：0.926，95%CI：0.881-0.974，p=0.0026）与 CTS 风险呈负相关。相反，CCL20、IL-2RB 和 IL-6 与 CTS 风险增加呈正相关。具体而言，CCL20（OR：1.072，95%CI：1.005-1.142，p=0.0334）、IL-2RB（OR：1.067，95%CI：1.001-1.137，p=0.0463）和 IL-6（OR：1.088，95%CI：1.005-1.177，p=0.0365）与 CTS 风险呈正相关。反向孟德尔随机化分析表明，CTS 和炎症细胞因子之间没有反向因果关系的证据。
根据这项研究，CTS 和某些炎症细胞因子之间存在因果关系，这表明这些细胞因子可能在 CTS 的病理生理学中具有重要作用。为了证实这些结果并研究这些细胞因子在 CTS 的发生和发展中的具体作用，还需要进一步研究。
