Sudden sensorineural hearing loss (SSNHL) is defined as a loss of at least 30 dB in three contiguous frequencies over 3 days or less [1]. The estimated incidence is between 5 and 20 per 100,000 persons per year in the United States [1]. The incidence rates per a population of 100,000 in Taiwan are 8.85 for men and 7.79 for women [2]. The detailed etiology and pathogenesis of SSNHL are still unclear. Potential causes may include viral infection, vascular disease, intracochlear membrane rupture, autoimmunity, and genetic factors. [3]. Histopathologic studies of SSNHL revealed changes in the cochlea, including atrophy of the organ of Corti and loss of cochlear neurons, which was the main finding in viral Inflammation [4]. However, there is no consensus, and the etiology and pathogenesis of SSNHL remain controversial.

Merchant et al. [5] revealed that a final common pathway for several possible etiologies of sudden sensorineural hearing loss may be the result of pathologic activation of cellular stress pathways involving nuclear factor kappa B (NF-kB) within the cochlea. Cortisol acts in the regulation of other glucocorticoid-responsive genes and is involved in interactions between the cortisol-glucocorticoid receptor complex and other transcription factors, such as NF-kB. The cortisol-glucocorticoid receptor complex also physically interacts with NF-kB to block its transcriptional activity leading to the anti-inflammatory effect [6].

Several factors related to the outcomes of SSNHL, including age, initial hearing loss severity and pattern, vertigo, and the time between onset and treatment, have been investigated [7,8,9]. Steroids (glucocorticoids) in either oral, intratympanic, or intravascular forms are the treatment of choice for SSNHL patients, but the outcome varies [7, 10]. The efficacy of glucocorticoids (GCs) in alleviating inflammatory disorders results from the pleiotropic effects of the glucocorticoid receptor (GR) on multiple signaling pathways [6]. The distribution of GRs in the cochlea appears to be subsite specific. GRs are expressed at highest concentrations with in the organ of Corti, followed by the spiral ganglion neurons (SGNs), and are present in lower concentration within the stria vascularis and fibrocytes of the lateral cochlear wall [11]. In an animal study, the authors found intense nuclear immunofluorescence at basal and apical SGN regions after GC administrated either via local or systemic route, which was greater than control tissue. And the GR activation of the SGNs was equivalent in both administration regimens [12]. The above findings indicate that GCs may bind to the nuclear GRs in the inner ear to perform the anti-inflammatory effect in SSNHL.

GR is a member of the steroid hormone receptor family of proteins [13]. GR binds with high affinity to cortisol in the cell, and the cortisol-GR complex inhibits inflammation through direct and indirect genomic effects and nongenomic mechanisms[6]. GR is known as nuclear receptor subfamily 3 Group C member 1 (NR3C1). The NR3C1 gene is located on chromosome 5q31–32. Variation in the structure and the expression of the gene generates diversity in glucocorticoid signaling [14]. However, there is little published literature about the relationship between the corticosteroid receptor gene and the outcomes of SSNHL. Kitoh et al. reported a marginal correlation between the single nucleotide polymorphism (SNP) of the NR3C1 gene (rs4912910) and steroid treatment outcomes in SSNHL patients [15]. Genetic polymorphisms of the NR3C1 gene might alter the affinity of GR to corticosteroids, affect the anti-inflammatory effect, and lead to a poorer outcome in SSNHL.

There is no doubt that the evaluation of genetic polymorphisms in SSNHL is important because identifying patients with genotypes with a poor outcome may help us develop optimal treatment strategies. In the present study, we hypothesize that the SNPs of the GR gene (i.e., the NR3C1 gene) may be crucial for the outcomes of SSNHL. The goal of this study was to understand the role of NR3C1 genetic polymorphisms in the outcomes of SSNHL after steroid treatment in Taiwan.