Inflammatory cytokines and carpal tunnel syndrome: A causal relationship revealed

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.