In the present study, we aimed to investigate, for the first time, the association between the risk of SSNHL and Ménière's disease and five oxidative stress-related genetic polymorphisms using a case–control study. No significant differences in the distribution of genotypes and allele frequencies of the polymorphisms described above were observed among SSNHL patients, Ménière's disease patients, and controls. No significant risk of SSNHL and Ménière's disease was observed for the five polymorphisms.
Recently, it was reported that the blood–labyrinth barrier is disrupted in at least one-third of patients with SSNHL, because gadolinium contrast agents injected intravenously appeared in the affected inner ear on magnetic resonance imaging (MRI) (Yoshida et al.
). MRI also revealed a weak blood–labyrinth barrier in ears affected by Ménière's disease compared with asymptomatic contralateral ears (Nakashima et al.
; Tagaya et al.
). As disruption of the blood–labyrinth barrier is associated with increased permeability of blood vessels in the inner ear and endothelium tight junctions, which leads to the disruption of the permeability of blood by ROS (Grammas et al.
), ROS may be involved in the pathology of SSNHL and Ménière's disease.
SOD enzymes catalyze the conversion of superoxide radicals to hydrogen peroxide. The SOD2 enzyme protects against damage caused by free radicals (Fortunato et al.
). It has been reported that Ala16Ala homozygotes may have higher SOD2 activity than Val16Val homozygotes (Sutton et al.
). The SOD2
Ala16Ala genotype is associated with an increased breast cancer risk, a high degree of carotid atherosclerosis, and exudative age-related macular degeneration in Japanese individuals, in whom allele Ala occurs less frequently than it does in Caucasians (Ambrosone et al.
; Kimura et al.
; Kakko et al.
). Hearing loss in Ménière's disease is associated with loss of spiral ganglion neurons and hair cells. In a guinea pig model of endolymphatic hydrops, oxidative stress mediated the loss of spiral ganglion neurons (Labbe et al.
). In the present study, Ménière's disease patients with a hearing level over 50 dB exhibited a higher minor-allele frequency compared with patients with a hearing level below 50 dB, suggesting that the SOD2
Val16Ala (rs4880) polymorphism is associated with progression of hearing loss in Ménière's disease.
Paraoxonases exert antioxidant activity and may protect against diseases, such as atherosclerosis, diabetes, Alzheimer dementia, and Parkinson disease (Mackness et al.
; Akhmedova et al.
; Janka et al.
; Fortunato et al.
gene family consists of PON1
, and PON3
, which are located on chromosome 7q21–q22 (Primo-Parmo et al.
). The PON1
192Arg, and, more recently, PON2
311Cys variants have been implicated in the oxidative damage associated with the pathogenesis of neurodegenerative diseases, such as Alzheimer disease and Parkinson disease (Carmine et al.
; Shi et al.
). The C allele of the PON2
Ser311Cys polymorphism is associated with a noise-induced hearing loss (Fortunato et al.
). A higher frequency of the minor allele of the PON1
Met55Leu polymorphism was observed in SSNHL cases with good recovery compared with those with poor recovery. However, as the frequency of the minor allele of this polymorphism is very small, that is, only four, further investigations using larger case samples are required to confirm the association between this polymorphism and hearing recovery in SSNHL.
Via its action in regulating the cellular levels of peroxide, GPX plays a critical role in minimizing the production of hydroxyl radical. Although there may be species differences, GPX appears to be expressed at comparatively high levels in the cochlea. GPX1
knockout mice exhibited auditory brainstem response thresholds that were up to 16 dB higher before noise exposure, and up to 15 dB greater noise-induced hearing loss, depending on test frequency, compared with controls (Ohlemiller et al.
). However, no association was found between the GPX
Pro198Leu polymorphism and the risk of SSNHL and Ménière's disease.
Generally, statistical power depends on the sample size, the significance criterion, and the effect size (Cohen, 1992
). The power level in the comparison of genotype distribution in each polymorphism in the present study varied between 0.019 and 1.0 and was below 0.8, with the exception of the cases of PON2
Ser311Cys and SOD2
Val16Ala. The observation that the genotype distribution for each polymorphism between controls and SSNHL or Ménière's disease was similar in this negative study may lower the effect size, leading to a low power level. This is the weakness of our study and these results need to be confirmed in larger series of patients in future studies.