Causal relationship between plasma metabolites and carpal tunnel syndrome risk: evidence from a mendelian randomization study.

IF 3.9 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Frontiers in Molecular Biosciences Pub Date : 2024-10-03 eCollection Date: 2024-01-01 DOI:10.3389/fmolb.2024.1431329

Wenbao Wu, Daofeng Fan, Chong Zheng, Binfu Que, Qing Qing Lian, Yangui Chen, Rui Qiu

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引用次数: 0

Abstract

Background: 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.

Methods: 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.

Results: 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 _FDR = 0.002), adenosine 5'-monophosphate (AMP) to phosphate ratio (OR [95% CI]:0.58 [0.45-0.74], p _FDR = 0.009), cysteinylglycine disulfide levels (OR [95% CI]: 0.85 [0.78-0.92], p _FDR = 0.047) and CTS was finally identified.

Conclusion: 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.

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血浆代谢物与腕管综合征风险之间的因果关系：泯灭随机研究的证据。

背景：腕管综合征（CTS）是一种常见的神经压迫症状，也是导致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了。本研究旨在揭示循环代谢物对 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，包括反方差加权、MR-Egger、加权中位数、简单模式和加权模型，研究了 1400 种代谢物与 CTS 发病风险之间的关联。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（SNPs）。CTS数据来自FinnGen联盟，其中包括11208例病例和195047例欧洲血统对照：双样本 MR 研究结果表明，77 种代谢物（代谢物比率）与 CTS 存在关联。经错误发现率（FDR）校正后，葡萄糖醛酸水平（奇数比（OR）[95% CI]：0.98 [0.97-0.99]，p FDR = 0.002）、5'-单磷酸腺苷（AMP）与磷酸盐比率（OR [95% CI]：0.58 [0.45-0.74]，p FDR = 0.009）、半胱氨酸二硫化物水平（OR [95% CI]：0.85 [0.78-0.92]，p FDR = 0.047）与 CTS 之间的因果关系最终被确定：综上所述，本研究结果表明，所鉴定的葡萄糖醛酸、AMP与磷酸盐的比率和半胱氨酰甘氨酸二硫化物水平可作为未来临床实践中筛查和预防CTS的代谢生物标志物，也可作为未来机制探索和药物靶点选择的候选分子。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Frontiers in Molecular Biosciences Biochemistry, Genetics and Molecular Biology-Biochemistry

CiteScore

7.20

自引率

4.00%

发文量

1361

审稿时长

14 weeks

期刊介绍： Much of contemporary investigation in the life sciences is devoted to the molecular-scale understanding of the relationships between genes and the environment — in particular, dynamic alterations in the levels, modifications, and interactions of cellular effectors, including proteins. Frontiers in Molecular Biosciences offers an international publication platform for basic as well as applied research; we encourage contributions spanning both established and emerging areas of biology. To this end, the journal draws from empirical disciplines such as structural biology, enzymology, biochemistry, and biophysics, capitalizing as well on the technological advancements that have enabled metabolomics and proteomics measurements in massively parallel throughput, and the development of robust and innovative computational biology strategies. We also recognize influences from medicine and technology, welcoming studies in molecular genetics, molecular diagnostics and therapeutics, and nanotechnology. Our ultimate objective is the comprehensive illustration of the molecular mechanisms regulating proteins, nucleic acids, carbohydrates, lipids, and small metabolites in organisms across all branches of life. In addition to interesting new findings, techniques, and applications, Frontiers in Molecular Biosciences will consider new testable hypotheses to inspire different perspectives and stimulate scientific dialogue. The integration of in silico, in vitro, and in vivo approaches will benefit endeavors across all domains of the life sciences.