Wang Jing, Li Fuyan, Ren Fuxin, Ma Wen, Liu Yuxi, Zhang Wenjing, Li Xi, Bi Yanfei, Xin Qian, Gao Fei
Department of Radiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, 324 Jing-Wu Road, Jinan, 250021, China.
Department of Otolaryngology, The Central Hospital of Jinan City, Shandong University, Jinan, China.
Mol Neurobiol. 2025 May 13. doi: 10.1007/s12035-025-05011-3.
This study aimed to investigate the relationship between GRM7 polymorphisms and the levels of glutamate (Glu) and glutathione (GSH) in bilateral auditory regions (ARs) of ARHL patients. Seventy-eight ARHL patients (mean age, 65.94 years ± 3.37 [SD]; 44 men) and 46 normal hearing (NH) controls (mean age, 65.72 years ± 2.32 [SD]; 28 men) were enrolled. Glu and GSH levels in bilateral ARs of all participants were measured and estimated by using magnetic resonance spectroscopy (MRS) and LCModel. In addition, we collected peripheral venous blood samples from all participants for DNA extraction and investigated polymorphisms in the GRM7 gene using TaqMan SNP genotyping. The results showed that Glu and GSH levels in bilateral ARs were significantly lower in GRM7 high-risk group compared with GRM7 low-risk group, regardless of disease status (all p < 0.001; all p = 0.001). Furthermore, GRM7 low-risk ARHL group had lower Glu levels in bilateral ARs than GRM7 low-risk NH group, whereas no difference was observed between NH and ARHL groups in high-risk (all p < 0.05; all p > 0.05). Finally, we found that Glu and GSH levels were positively correlated only in the low-risk NH group (r = 0.536 p = 0.007; r = 0.545 p = 0.006). The glutamatergic dysfunction in ARs may be associated with GRM7 polymorphisms, and redox reactions are involved in regulating the glutamatergic abnormalities. The TT genotype of GRM7 rs11928865 SNP is more vulnerable to damage from the antioxidant and the glutamatergic system.
本研究旨在探讨GRM7基因多态性与老年聋（ARHL）患者双侧听觉区域（ARs）中谷氨酸（Glu）和谷胱甘肽（GSH）水平之间的关系。纳入了78例ARHL患者（平均年龄65.94岁±3.37[标准差]；44例男性）和46例听力正常（NH）对照者（平均年龄65.72岁±2.32[标准差]；28例男性）。使用磁共振波谱（MRS）和LCModel测量并评估了所有参与者双侧ARs中的Glu和GSH水平。此外，我们采集了所有参与者的外周静脉血样本用于DNA提取，并使用TaqMan SNP基因分型技术研究GRM7基因的多态性。结果显示，无论疾病状态如何，GRM7高风险组双侧ARs中的Glu和GSH水平均显著低于GRM7低风险组（所有p<0.001；所有p=0.001）。此外，GRM7低风险ARHL组双侧ARs中的Glu水平低于GRM7低风险NH组，而高风险组中NH组和ARHL组之间未观察到差异（所有p<0.05；所有p>0.05）。最后，我们发现仅在低风险NH组中Glu和GSH水平呈正相关（r=0.536，p=0.007；r=0.545，p=0.006）。ARs中的谷氨酸能功能障碍可能与GRM7基因多态性有关，氧化还原反应参与调节谷氨酸能异常。GRM7 rs11928865 SNP的TT基因型更容易受到抗氧化剂和谷氨酸能系统损伤的影响。
