筛选血浆蛋白用于腕管综合征的推定药物靶点。

IF 3.6 4区 医学 Q3 CELL BIOLOGY
Cellular and Molecular Neurobiology Pub Date : 2023-11-01 Epub Date: 2023-10-25 DOI:10.1007/s10571-023-01428-3
Bai-Xue Han, Tian-Ye Huang, Qi-Gang Zhao, Shan-Shan Yan, Qian Xu, Xin-Ling Ma, Yuan Luo, Yu-Fang Pei
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引用次数: 0

摘要

腕管综合征(CTS)是最常见的与工作相关的肌肉骨骼疾病之一。本研究试图确定CTS的假定致病蛋白。我们进行了两个样本的孟德尔随机化(MR)分析,以评估2859种血浆蛋白(N = 35559)和CTS(N = 1239680)。然后我们使用独立的血浆蛋白质组GWAS(N = 10708)。进行灵敏度分析以验证MR结果的稳健性。进行了多变量MR和中介分析,以评估身体质量指数(BMI)、2型糖尿病(T2D)和手臂组织成分对假定因果蛋白和CTS之间关系的中介作用。共定位分析用于检查所鉴定的蛋白质和CTS是否共享因果变异。最后,我们评估了已鉴定蛋白质的可药用性。10种血浆蛋白被鉴定为CTS的假定因果标志物,包括sCD14、PVR、LTOR3、CTSS、SIGIRR、IFNL3、ASPN、TM11D、ASIP和ITIH1。敏感性分析和反向MR分析验证了其因果效应的稳健性。臂组织组成、BMI和T2D可能在ASIP、TM11D、IFNL3、PVR和LTOR3与CTS的因果关系中发挥完全/部分中介作用。共定位分析支持ASPN和sCD14与CTS的相关性。可药用性评估表明sCD14、CTSS、TM11D和IFNL3是潜在的药物治疗靶点。本研究确定了几种与CTS风险有因果关系的潜在血浆蛋白,为蛋白介导的CTS的发病机制提供了新的见解,并为新疗法提供了潜在的靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Screening Plasma Proteins for the Putative Drug Targets for Carpal Tunnel Syndrome.

Screening Plasma Proteins for the Putative Drug Targets for Carpal Tunnel Syndrome.

Carpal tunnel syndrome (CTS) is one of the most common work-related musculoskeletal disorders. The present study sought to identify putative causal proteins for CTS. We conducted a two-sample Mendelian randomization (MR) analysis to evaluate the causal association between 2859 plasma proteins (N = 35,559) and CTS (N = 1,239,680) based on the published GWAS summary statistics. Then we replicated the significant associations using an independent plasma proteome GWAS (N = 10,708). Sensitivity analyses were conducted to validate the robustness of MR results. Multivariate MR and mediation analyses were conducted to evaluate the mediation effects of body mass index (BMI), type 2 diabetes (T2D), and arm tissue composition on the association between putative causal proteins and CTS. Colocalization analysis was used to examine whether the identified proteins and CTS shared causal variant(s). Finally, we evaluated druggability of the identified proteins. Ten plasma proteins were identified as putative causal markers for CTS, including sCD14, PVR, LTOR3, CTSS, SIGIRR, IFNL3, ASPN, TM11D, ASIP, and ITIH1. Sensitivity analyses and reverse MR analysis validated the robustness of their causal effects. Arm tissue composition, BMI, and T2D may play a fully/partial mediating role in the causal relationships of ASIP, TM11D, IFNL3, PVR, and LTOR3 with CTS. The association of ASPN and sCD14 with CTS were supported by colocalization analysis. Druggability assessment demonstrated that sCD14, CTSS, TM11D, and IFNL3 were potential drug therapeutic targets. The present study identified several potential plasma proteins that were causally associated with CTS risk, providing new insights into the pathogenesis of protein-mediated CTS and offering potential targets for new therapies.

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来源期刊
CiteScore
7.70
自引率
0.00%
发文量
137
审稿时长
4-8 weeks
期刊介绍: Cellular and Molecular Neurobiology publishes original research concerned with the analysis of neuronal and brain function at the cellular and subcellular levels. The journal offers timely, peer-reviewed articles that describe anatomic, genetic, physiologic, pharmacologic, and biochemical approaches to the study of neuronal function and the analysis of elementary mechanisms. Studies are presented on isolated mammalian tissues and intact animals, with investigations aimed at the molecular mechanisms or neuronal responses at the level of single cells. Cellular and Molecular Neurobiology also presents studies of the effects of neurons on other organ systems, such as analysis of the electrical or biochemical response to neurotransmitters or neurohormones on smooth muscle or gland cells.
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