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剖析梅尼埃病和前庭性偏头痛中的生物钟与Toll样受体基因改变

Dissecting the Circadian Clock and Toll-like Receptor Gene Alterations in Meniere's Disease and Vestibular Migraine.

作者信息

Yang Ming-Yu, Wu Ching-Nung, Lin Yu-Tsai, Tsai Ming-Hsien, Hwang Chung-Feng, Yang Chao-Hui

机构信息

Department of Otolaryngology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.

Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan.

出版信息

Otolaryngol Head Neck Surg. 2025 Mar;172(3):999-1005. doi: 10.1002/ohn.1085. Epub 2024 Dec 15.

DOI:10.1002/ohn.1085
PMID:39675041
Abstract

OBJECTIVE

To investigate alterations in the expression of circadian clock and Toll-like receptor (TLR) genes in peripheral blood (PB) leukocytes of patients with Meniere's disease (MD) and vestibular migraine (VM), and determine whether these gene expressions can differentiate MD from VM.

STUDY DESIGN

Observational prospective study.

SETTING

Tertiary academic medical center.

METHODS

PB leukocytes were collected from patients diagnosed with MD and VM during recent vertigo attacks, as well as from healthy controls. The expression levels of 9 circadian clock genes and 6 TLR genes were analyzed using real-time quantitative reverse transcriptase-polymerase chain reaction.

RESULTS

Sixty-nine participants were enrolled, including 28 patients with MD, 14 patients with VM, and 27 healthy controls. Both MD and VM groups showed lower expression of PER1 compared to the control group (P < .01). The VM group exhibited significantly lower expression of PER1, PER2, CRY1, BMAL1, CLOCK, and TIM compared to the MD group (all P < .001). The MD group had higher TLR9 expression than the control group, and elevated TLR4, TLR8, and TLR9 expression compared to the VM group (P < .05). In the VM group, patients with severe dizziness handicaps had significantly lower expression of PER2, CRY1, CRY2, and CK1ε compared to those with mild to moderate handicaps (P < .05).

CONCLUSION

This study identifies distinct alterations in the circadian clock and TLR gene expression in MD and VM, suggesting potential differences in the pathogenesis of these 2 vertiginous disorders and highlighting the possibility of these gene expressions as biomarkers for differentiation.

摘要

目的

研究梅尼埃病(MD)和前庭性偏头痛(VM)患者外周血(PB)白细胞中昼夜节律钟基因和Toll样受体(TLR)基因表达的变化,并确定这些基因表达是否能区分MD和VM。

研究设计

观察性前瞻性研究。

研究地点

三级学术医学中心。

方法

在近期眩晕发作期间,从诊断为MD和VM的患者以及健康对照者中采集PB白细胞。使用实时定量逆转录聚合酶链反应分析9种昼夜节律钟基因和6种TLR基因的表达水平。

结果

共纳入69名参与者,包括28例MD患者、14例VM患者和27名健康对照者。与对照组相比,MD组和VM组的PER1表达均较低(P < 0.01)。与MD组相比,VM组的PER1、PER2、CRY1、BMAL1、CLOCK和TIM表达明显较低(所有P < 0.001)。MD组的TLR9表达高于对照组,与VM组相比,TLR4、TLR8和TLR9表达升高(P < 0.05)。在VM组中,与轻度至中度残疾患者相比,重度头晕残疾患者的PER2、CRY1、CRY2和CK1ε表达明显较低(P < 0.05)。

结论

本研究发现MD和VM患者的昼夜节律钟和TLR基因表达存在明显差异,提示这两种眩晕疾病的发病机制可能存在潜在差异,并突出了这些基因表达作为鉴别生物标志物的可能性。

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