Polymorphisms in Genes Involved in Inflammatory Pathways in Patients with Sudden Sensorineural Hearing Loss

Abstract

Although the etiology of idiopathic sudden sensorineural hearing loss (SSNHL) remains unclear, the pathologically increased permeability of blood vessels, elucidated by gadolinium-enhanced magnetic resonance imaging (MRI), suggests the involvement of inflammation. Because SSNHL is considered a multifactorial disease, possibly caused by interactions between genetic factors and environmental factors, the authors investigated the associations of polymorphisms of inflammatory mediator genes with susceptibility to SSNHL. The authors compared 72 patients affected by SSNHL and 2010 adults (1010 men and 1000 women; mean age 59.2 years; range 40-79) who participated in the National Institute for Longevity Sciences Longitudinal Study of Aging. Multiple logistic regression was used to obtain odds ratios (ORs) for SSNHL in subjects with polymorphisms in the genes IL-6 C - 572G, IL-4R G1902A, IL-10 A - 592C, TNFα C - 863A, TNFRSF1B G593A, VEGF C936T, VEGF C - 2578A, and VEGF G - 1154A, with adjustment for age, gender, and any history of hypertension, diabetes, or dyslipidemia. The per-allele OR for the risk of SSNHL in subjects bearing IL-6 C - 572G was 1.480 (95% confidence interval [CI], 1.037-2.111) in model 1 (no adjustment), 1.463 (CI, 1.022-2.094) in model 2 (adjusted for age and gender), and 1.460 (CI, 1.016-2.097) in model 3 (adjusted for age, gender, and a history of hypertension, diabetes, or dyslipidemia). Under the dominant model of inheritance, the ORs were 1.734 (CI, 1.080-2.783) in model 1, 1.690 (CI, 1.050-2.721) in model 2, and 1.669 (CI, 1.035-2.692) in model 3. The remaining seven polymorphisms failed to show any associations with the risk of SSNHL. These data need to be confirmed on larger series of patients. In conclusion, the IL-6 C - 572G polymorphism is associated with a risk of SSNHL. Because permeability of blood vessels in the inner ear is frequently increased in patients with SSNHL, inflammation of the inner ear might be involved.

Coexistence of IL-6 -572C/G and ICAM-1 K469E Polymorphisms among Patients with Sudden Sensorineural Hearing Loss

“…We, therefore, investigated the potential association between IL-6 -572C/G polymorphism and SSNHL. Our results were consistent with a previous study which indicated that IL-6 -572C/G polymorphism might influence the susceptibility to SSNHL in Japanese patients (Hiramatsu et al 2012). The gene encoding ICAM-1 is located on chromosome 19p13.2.…”

“…IL-6 promotes atherosclerosis by impairing vascular endothelial cells and contributing to endothelial activation (Papanicolaou et al 1998). Elevated serum concentration of IL-6 has been reported in cardiovascular events and SSNHL (Hou et al 2008;Hiramatsu et al 2012). There is a polymorphism in the promoter region at position -572 of the IL-6 gene, which is C/G.…”

“…This SNP in promoter region is highly possible to induce its expression abnormality, although need more experimental verification. A significant association between SSNHL and the IL-6 -572C/G polymorphism was found in Japanese patients (Hiramatsu et al 2012). In addition, several previous studies indicated that IL-6 and ICAM-1 gene polymorphisms act synergistically in some diseases (Kitawaki et al 2006;Lv et al 2012).…”

New Prognostic Parameters of Sudden Hearing Loss: Neutrophil to Lymphocyte Ratio and Platelet to Lymphocyte Ratio

“…Bazı çalışamalarda, AİK nedeni olarak kronik enfeksiyon üzerinde durulmaktadır (19) . Kronik inflamasyon iskemik hasar oluşturararak mikrovasküler zedelenme ve aterogeneze ortam hazırlar.…”

The Significance of Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio as Markers for Prognosis in Idiopathic Sudden Sensorineural Hearing Loss

“…However, there is no conclusive evidence for any particular hypothesis [2][3][4]. The cause of ISSNHL has been focused on chronic inflammation recently [5]. Chronic inflammation can cause microvascular injury and atherogenesis, which is increasing ischemic risk in a direct manner [6].…”