Wu Wenbao, Fan Daofeng, Zheng Chong, Que Binfu, Lian Qing Qing, Chen Yangui, Qiu Rui
Department of Acupuncture and Moxibustion, Longyan First Hospital Affiliated to Fujian Medical University, Longyan, China.
Department of Neurology, Longyan First Hospital Affiliated to Fujian Medical University, Longyan, China.
Front Mol Biosci. 2024 Oct 3;11:1431329. doi: 10.3389/fmolb.2024.1431329. eCollection 2024.
Carpal tunnel syndrome (CTS) is a common symptom of nerve compression and a leading cause of pain and hand dysfunction. However, the underlying biological mechanisms are not fully understood. The aim of this study was to reveal the causal effect of circulating metabolites on susceptibility to CTS.
We employed various Mendelian randomization (MR) methods, including Inverse Variance Weighted, MR-Egger, Weighted Median, Simple Mode, and Weighted Model, to examine the association between 1,400 metabolites and the risk of developing CTS. We obtained Single-nucleotide polymorphisms (SNPs) associated with 1,400 metabolites from the Canadian Longitudinal Study on Aging (CLSA) cohort. CTS data was derived from the FinnGen consortium, which included 11,208 cases and 1,95,047 controls of European ancestry.
The results of the two-sample MR study indicated an association between 77 metabolites (metabolite ratios) and CTS. After false discovery rate (FDR) correction, a strong causal association between glucuronate levels (odd ratio (OR) [95% CI]: 0.98 [0.97-0.99], p = 0.002), adenosine 5'-monophosphate (AMP) to phosphate ratio (OR [95% CI]:0.58 [0.45-0.74], p = 0.009), cysteinylglycine disulfide levels (OR [95% CI]: 0.85 [0.78-0.92], p = 0.047) and CTS was finally identified.
In summary, the results of this study suggest that the identified glucuronate, the ratio of AMP to phosphate, and cysteinylglycine disulfide levels can be considered as metabolic biomarkers for CTS screening and prevention in future clinical practice, as well as candidate molecules for future mechanism exploration and drug target selection.
腕管综合征（CTS）是神经受压的常见症状，也是疼痛和手部功能障碍的主要原因。然而，其潜在的生物学机制尚未完全明确。本研究的目的是揭示循环代谢物对CTS易感性的因果效应。
我们采用了多种孟德尔随机化（MR）方法，包括逆方差加权法、MR-Egger法、加权中位数法、简单模式法和加权模型法，来检验1400种代谢物与患CTS风险之间的关联。我们从加拿大老龄化纵向研究（CLSA）队列中获得了与1400种代谢物相关的单核苷酸多态性（SNP）。CTS数据来自芬兰基因联盟，其中包括11208例病例和195047例欧洲血统对照。
两样本MR研究结果表明，77种代谢物（代谢物比率）与CTS之间存在关联。经过错误发现率（FDR）校正后，最终确定葡萄糖醛酸盐水平（优势比（OR）[95%置信区间]：0.98[0.97 - 0.99]，p = 0.002）、5'-单磷酸腺苷（AMP）与磷酸盐的比率（OR[95%置信区间]：0.58[0.45 - 0.74]，p = 0.009）、半胱氨酰甘氨酸二硫化物水平（OR[95%置信区间]：0.85[0.78 - 0.92]，p = 0.047）与CTS之间存在强因果关联。
总之，本研究结果表明，所确定的葡萄糖醛酸盐、AMP与磷酸盐的比率以及半胱氨酰甘氨酸二硫化物水平，在未来临床实践中可被视为CTS筛查和预防的代谢生物标志物，以及未来机制探索和药物靶点选择的候选分子。
