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探究循环炎症蛋白与耳鸣之间的因果关系:孟德尔随机化研究的见解

Investigating the causal relationship between circulating inflammatory proteins and tinnitus: Insights from a Mendelian Randomization study.

作者信息

He Shichun, Wei Meiqi, Meng Deyu, Lv Zongnan, Yang Guang, Wang Ziheng

机构信息

Graduate School of Health Management, Keio University, Kanagawa, Japan; Division of Computational Biology, Chinese Center of Exercise Epidemiology, Northeast Normal University, Renmin Street, Changchun, 130024, Jilin, China.

School of Physical Education, Changchun University, 6543 Satellite Road, Changchun, 130022, Jilin, China; Division of Computational Biology, Chinese Center of Exercise Epidemiology, Northeast Normal University, Renmin Street, Changchun, 130024, Jilin, China.

出版信息

Hear Res. 2025 Sep;465:109300. doi: 10.1016/j.heares.2025.109300. Epub 2025 Jul 9.

Abstract

Tinnitus, a condition characterized by the perception of ringing in the ears, significantly impacts quality of life, yet its underlying biological mechanisms remain poorly understood. Emerging evidence suggests a role for inflammation in tinnitus pathophysiology. This study employs a bidirectional two-sample Mendelian Randomization (MR) approach to investigate the causal relationship between circulating inflammatory proteins and tinnitus. Genetic data from large-scale pQTL and GWAS datasets were analyzed to identify potential causal links. The results reveal that elevated levels of CCL19, CXCL11, and TNFSF12 are positively associated with tinnitus risk, while CD40L and IL-10 exhibit protective effects. Reverse MR analysis suggests that tinnitus may weakly influence levels of Cystatin D, IL-18, and MCP-1, though these associations require further validation. These findings provide novel insights into the inflammatory pathways involved in tinnitus, paving the way for targeted therapeutic strategies and future research into anti-inflammatory interventions.

摘要

耳鸣是一种以耳部出现耳鸣为特征的病症,严重影响生活质量,但其潜在的生物学机制仍知之甚少。新出现的证据表明炎症在耳鸣病理生理学中发挥作用。本研究采用双向两样本孟德尔随机化(MR)方法来研究循环炎症蛋白与耳鸣之间的因果关系。分析了来自大规模蛋白质定量性状位点(pQTL)和全基因组关联研究(GWAS)数据集的遗传数据,以确定潜在的因果联系。结果显示,CCL19、CXCL11和TNFSF12水平升高与耳鸣风险呈正相关,而CD40L和IL-10具有保护作用。反向MR分析表明,耳鸣可能对胱抑素D、IL-18和单核细胞趋化蛋白-1(MCP-1)水平有微弱影响,不过这些关联需要进一步验证。这些发现为耳鸣涉及的炎症途径提供了新的见解,为靶向治疗策略以及抗炎干预措施的未来研究铺平了道路。

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