Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi. 2026 Apr 20;44(4):241-246. doi: 10.3760/cma.j.cn121094-20250704-00267.
ABSTRACT
Objective: To evaluate the causal association between serum albumin and carpal tunnel syndrome (CTS) and to investigate the mediating role of leptin in this relationship. Methods: In April 2025, data on serum albumin, leptin (adjusted for body mass index), and CTS from Genome-Wide Association Studies (GWAS) and FinnGen public databases were collected for a two-way, two-sample Mendelian randomization (MR) analysis. Causal analyses were performed using inverse variance weighted (IVW), weighted median estimator, MR-Egger, simple mode, and weighted mode methods. The robustness of the results was tested using Cochran’s Q statistic, MR-Egger intercept test, Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) test. A two-step approach was used to analyze the mediating effect of leptin between serum albumin and CTS. Results: The IVW analysis showed that elevated serum albumin levels significantly increased the risk of CTS (OR=1.18, 95%CI: 1.00-1.38, P=0.045), and the results from the weighted median estimator and weighted mode method were consistent with the IVW direction and the differences were statistically significant (P<0.05). Mediation analysis revealed a significant negative causal effect between serum albumin and leptin (OR=0.44, 95%CI: 0.28-0.68, P<0.001), and elevated leptin levels significantly reduced the risk of CTS (OR=0.79, 95%CI: 0.68-0.94, P=0.006). Leptin played a key mediating role in the path of serum albumin affecting CTS (β(indirect)=0.190, P=0.027), with a mediation proportion of 118%. Reverse MR analysis showed that the causal effect of CTS on serum albumin was not statistically significant (OR=1.00, 95% CI: 0.97-1.04, P=0.889). There were no statistically significant differences in the heterogeneity test (Cochran’s Q=20.68, P=0.079) and multi-effect test (MR-Egger intercept value -0.004, P=0.684; MR-PRESSO global P=0.067) . Conclusion: There is a positive causal relationship between serum albumin level and the risk of CTS, and leptin level plays an important mediating role in this pathway, suggesting that albumin may indirectly increase the risk of CTS through the modulation of leptin, and provide new genetic clues for the identification of people at high risk of CTS.
PMID:42092244 | DOI:10.3760/cma.j.cn121094-20250704-00267
