Association of GRM7 Polymorphisms with Bilateral Auditory Regions Glutamate and Coupling with Glutathione in ARHL Patients.

Abstract

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_glu < 0.001; all p_gsh = 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_glu < 0.05; all p_glu > 0.05). Finally, we found that Glu and GSH levels were positively correlated only in the low-risk NH group (r_left = 0.536 p = 0.007; r_right = 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.