Decreased disulphide/thiol ratio in patients with autosomal recessive non-syndromic hearing loss

Introduction: Oxidative stress plays a key role in the formation of age-related, noise-induced and drug-induced hearing loss. Thiols are organic compounds which can react with free radicals to protect against tissue and cell damage caused by reactive oxygen. There are no studies in literature on the association between autosomal recessive non-syndromic hearing loss(ARNSHL) including GJB2 and non-GJB2 mutations and thiol-disulphide balance. In this study, we aim to assess whether thiol-disulphide balance is disrupted in patients with ARNSHL.

Methods: Thirty-one ARNSHL patients and thirty-one healthy controls were included in this study. Patients whose parents were first degree cousins and who had at least two congenital hearing loss in the same family were included in the study. Audiological tests included air - bone pure tone audiometry and auditory brain stem response. GJB2 gene analysis was performed using sanger sequence method. Tests of thiol/disulphide homeostasis were conducted using the automated spectrophotometric method. We first investigated whether there was a significant difference between ARNSHL patients and healthy controls. Then, in order to determine the differential effect of the GJB2 gene mutations and non-GJB2 gene mutations on the thiol-disulphide balance, subjects were divided into three groups: Group 1 included patients with GJB2 mutations; Group 2 included patients with non-GJB2 mutations; Group 3 included healthy subjects.

Results: Patients with ARNSHL had significantly higher native thiol (411.6 ± 54.3 μmol/l vs. 368.0 ± 64.3 μmol/l, p = 0.006), total thiol levels (440.3 ± 56.2 μmol/l vs. 402.4 ± 65.9 μmol/l, p = 0.018), and lower disulphide levels (14.3 ± 5.7 μmol/l) vs. (17.1 ± 4.9 μmol/l), (p = 0.043) compared to the control group. Moreover, disulphide /native thiol (p < 0.001) and disulphide/total thiol (p < 0.001) were also detected lower in the ARNSHL group compared to the control group. Thiol-disulphide hemostasis parameters between all three groups showed that the native thiol and total thiol were increased in the Group 1 and Group 2. The disulphide levels decreased in Group 1 and 2, although not statistically significant.

Conclusion: It was shown that thiol levels increased and disulphide levels decreased in patients with autosomal recessive non-syndromic hearing loss. It also may suggest that there is a reverse association between ARNSHL and oxidative stress. Further studies are needed on whether or not ARNSHL cause oxidative stress limited to the inner ear and cochlea.