LINE-1 global DNA methylation, iron homeostasis genes, sex and age in sudden sensorineural hearing loss (SSNHL).

BACKGROUND: Sudden sensorineural hearing loss (SSNHL) is an abrupt loss of hearing, still idiopathic in most of cases. Several mechanisms have been proposed including genetic and epigenetic interrelationships also considering iron homeostasis genes, ferroptosis and cellular stressors such as iron excess and dysfunctional mitochondrial superoxide dismutase activity. RESULTS: We investigated 206 SSNHL patients and 420 healthy controls for the following genetic variants in the iron pathway: SLC40A1 - 8CG (ferroportin; FPN1), HAMP - 582AG (hepcidin; HEPC), HFE C282Y and H63D (homeostatic iron regulator), TF P570S (transferrin) and SOD2 A16V in the mitochondrial superoxide dismutase-2 gene. Among patients, SLC40A1 - 8GG homozygotes were overrepresented (8.25% vs 2.62%; P = 0.0015) as well SOD2 16VV genotype (32.0% vs 24.3%; P = 0.037) accounting for increased SSNHL risk (OR = 3.34; 1.54-7.29 and OR = 1.47; 1.02-2.12, respectively). Moreover, LINE-1 methylation was inversely related (r2 = 0.042; P = 0.001) with hearing loss score assessed as pure tone average (PTA, dB HL), and the trend was maintained after SLC40A1 - 8CG and HAMP - 582AG genotype stratification (ΔSLC40A1 = + 8.99 dB HL and ΔHAMP = - 6.07 dB HL). In multivariate investigations, principal component analysis (PCA) yielded PC1 (PTA, age, LINE-1, HAMP, SLC40A1) and PC2 (sex, HFEC282Y, SOD2, HAMP) among the five generated PCs, and logistic regression analysis ascribed to PC1 an inverse association with moderate/severe/profound HL (OR = 0.60; 0.42-0.86; P = 0.0006) and with severe/profound HL (OR = 0.52; 0.35-0.76; P = 0.001). CONCLUSION: Recognizing genetic and epigenetic biomarkers and their mutual interactions in SSNHL is of great value and can help pharmacy science to design by pharmacogenomic data classical or advanced molecules, such as epidrugs, to target new pathways for a better prognosis and treatment of SSNHL.

The Expression Levels of MicroRNAs Differentially Expressed in Sudden Sensorineural Hearing Loss Patients' Serum Are Unchanged for up to 12 Months after Hearing Loss Onset.

Sudden sensorineural hearing loss (SSNHL) is an acquired idiopathic hearing loss. Serum levels of small, non-coding RNAs and microRNAs (miRNAs) miR-195-5p/-132-3p/-30a-3p/-128-3p/-140-3p/-186-5p/-375-3p/-590-5p are differentially expressed in SSNHL patients within 28 days of hearing loss onset. This study determines if these changes persist by comparing the serum miRNA expression profile of SSNHL patients within 1 month of hearing loss onset with that of patients 3-12 months after hearing loss onset. We collected serum from consenting adult SSNHL patients at presentation or during clinic follow-up. We matched patient samples drawn 3-12 months after hearing loss onset (delayed group, n = 9 patients) by age and sex to samples drawn from patients within 28 days of hearing loss onset (immediate group, n = 14 patients). We compared the real-time PCR-determined expression levels of the target miRNAs between the two groups. We calculated the air conduction pure-tone-averaged (PTA) audiometric thresholds in affected ears at the initial and final follow-up visits. We undertook inter-group comparisons of hearing outcome status and initial and final PTA audiometric thresholds. There was no significant inter-group difference in miRNA expression level, hearing recovery status and initial and final affected ear PTA audiometric thresholds.

Glucocorticoid receptor (NR3C1) genetic polymorphisms and the outcomes of sudden sensorineural hearing loss.

BACKGROUND: The glucocorticoid receptor gene (NR3C1) encodes the receptor to which cortisol and other glucocorticoids bind. Steroids in either oral, intratympanic, or intravascular forms are the treatment of choice for sudden sensorineural hearing loss (SSNHL), but the outcome varies. The outcomes of SSNHL have been investigated for related factors, including age, initial hearing loss severity and pattern, vertigo, genetic variations, and the time between onset and treatment. The objective of the present study was to analyze the association of genetic polymorphisms of NR3C1 with the outcomes of SSNHL. MATERIALS AND METHODS: We conducted a comparison study of 93 cases with a poor outcome (control) and 100 cases with a good outcome (case) in SSNHL patients. Six single nucleotide polymorphisms (SNPs) were selected. The genotypes were determined using TaqMan technology. RESULTS: The heterozygous AT genotype of rs17100289 was associated with a poor outcome in comparison with the major homozygous AA genotype after adjustments for age and sex (OR = 0.50; 95% CI 0.26-0.95; P = 0.035) in SSNHL patients. The CT genotype of rs4912912 was also associated with a poor outcome compared with the major homozygous TT genotype after the adjustments (OR = 0.47; 95% CI 0.24-0.92; P = 0.026). CONCLUSION: These results suggest that NR3C1 genetic polymorphisms may influence the outcomes of SSNHL.

Myosin Mutations and Sudden Sensorineural Hearing Loss: Results of Whole Exome Sequencing.

OBJECTIVE: Idiopathic sudden sensorineural hearing loss (ISSNHL) affects 66,000 patients per year in the United States. Genetic mutations have been associated with progressive hearing loss; however, genetic mutations associated with ISSNHL have not been identified. METHODS: A prospective cohort study of adults older than 18 years presenting with ISSNHL at a tertiary academic medical center. Whole exome sequencing (WES) was conducted using Genome Analysis Toolkit best practices. An automated diagnostic screen employing a variety of models for pathogenicity was conducted across all genes with no specific targets. Candidate pathogenic variants were reviewed by a team of geneticists and clinicians. Variants were crossed-referenced with 92 known hearing loss associated genes. RESULTS: Twenty-nine patients with SSNHL were screened using WES. The average age of patients was 53 ± 17.1 years, and most patients were White (62%) and men (55%). The mean pure tone average was 64.8 ± 31.3 dB for the affected ear. Using a 0.1% allele frequency screen, 12 (41%) cases had a mutation in any of the nine selected myosin genes. When we restrict to singletons (allele frequency = 0%), 21% (n = 6) of cases have qualifying variants, whereas only 3.8% (n = 481) of 12,577 healthy controls carry qualifying variants (p < 0.01). Most mutations (80%) were missense mutations. Of the novel mutations, one was a frameshift mutation, and two were a stop-gained function. Three were missense mutations. CONCLUSION: Myosin mutations may be associated with ISSNHL. However, larger population screening is needed to confirm the association of myosin mutation with ISSNHL and steroid responsiveness.

Uncovering Novel Prognostic Factors of Sudden Sensorineural Hearing Loss by Whole-Genome Sequencing of Cell-Free DNA.

BACKGROUND: Sudden sensorineural hearing loss is a common disease with several etiologic hypotheses, such as infection, vascular occlusion, inflammation, oxidative stress, etc. Studies have reported that the concentration of cell-free DNA in plasma will elevate in these situations. Former studies have reported that the whole-genome sequencing of cell-free DNA has high accuracy and sensitivity in inferring gene expressions. In this study, we plan to use the whole-genome sequencing of cell-free DNA to uncover novel prognostic factors of sudden sensorineural hearing loss and provide new insight into the clinical application of cell-free DNA. METHODS: In this study, 84 sudden sensorineural hearing loss patients (47 in recovery group and 37 in no-recovery group) were enrolled. After whole-genome sequencing of the cell-free DNA, the protein-protein interaction network was constructed using the differentially expressed genes. Multinomial logistics regression analysis was used to analyze the prognostic factors of hearing improvement. RESULTS: In this study, we found distinct patterns of expressed and unexpressed genes in cell-free DNA sequence read depth coverage in sudden sensorineural hearing loss patients. The top centrality hub genes IGF1, NOTCH1, APOE, FAM3C, RPS6KB1, and RELB were identified from the protein-protein interaction network. Multinomial logistics regression analysis demonstrated that the coverage patterns of 3 key differentially expressed genes (NOTCH1, APOE, and RELB) are significantly different in sudden sensorineural hearing loss with and without hearing recovery. CONCLUSION: The cell-free DNA could have more applications in diverse diseases, and the coverage patterns of 3 differentially expressed genes (NOTCH1, APOE, and RELB) are independent prognostic factors of sudden sensorineural hearing loss. Their expression levels may play a critical role in the hearing improvement of sudden sensorineural hearing loss patients.

The association of genetic polymorphisms in interleukin-1 receptors type 1 and type 2 with sudden sensorineural hearing loss in a Taiwanese population: a case control study.

BACKGROUND: Sudden sensorineural hearing loss (SSNHL) is a disease with an unknown etiology; damage to the auditory nerve from inflammation due to viral infection or vascular incidents has been implicated. According to several studies, cytokines, including interleukins, are associated with SSNHL in terms of serum expression and genetic polymorphisms. Interleukin-1 (IL-1) plays a key role in inflammation and may be associated with SSNHL. This study analyzed the association of single nucleotide polymorphisms (SNPs) of IL-1 receptor (IL-1R) genes with SSNHL in Taiwan. METHODS: We conducted a case-control study involving 401 patients with SSNHL and 730 healthy controls. Four SNPs (IL-1R type 1 gene [IL1R1] [rs3917225 and rs2234650] and IL-1R type 2 gene [IL1R2] [rs4141134 and rs2071008]) were selected. The genotypes were determined using the TaqMan assay. The Hardy-Weinberg equilibrium (HWE) was tested for each SNP, and genetic effects were evaluated. RESULTS: The TT genotype of rs2234650 had an adjusted odds ratio (OR) of 2.988 (95% confidence interval [95% CI] 1.27-6.82) (P = 0.012) compared with the CC genotype in patients with SSNHL. The SNP rs2234650 was associated with SSNHL in the recessive model (TT vs. CC + CT, P = 0.0206, OR = 2.681). The CT genotype of rs4141134 had an adjusted OR of 3.860 (95% CI 2.01-7.44; P < 0.0001) compared with the TT genotype, in patients with SSNHL. The SNP rs4141134 was associated with SSNHL under the dominant model (CC + CT vs. TT, P < 0.0001, OR = 4.087). CONCLUSION: These findings suggest that IL1R1 and IL1R2 gene polymorphisms may contribute to an increased risk of SSNHL in Taiwan.

Genetic Susceptibility Study of Chinese Sudden Sensorineural Hearing Loss Patients with Vertigo.

OBJECTIVE: To investigate the genetic causes of sudden sensorineural hearing loss (SSNHL) patients in China. This study focused on analyzing variations of coding sequence of common genes related to deafness, revealing the molecular pathogenesis of sudden deafness from a genomics perspective, discovering molecular markers associated with the onset of deafness, and then supplying prevention to high-risk populations, classifying disease according to accurate etiology, and choosing a much more precision therapy. METHODS: We retrospectively analyzed the clinical characteristics of 51 patients diagnosed as SSNHL with vertigo treated in the Chinese PLA General Hospital. In this study, mutation screening of 307 nuclear genes and mitochondrial genome responsible for human or mouse deafness was performed on the 51 cases of unilateral sudden deafness patients with vertigo. RESULTS: We identified 51 cases of unilateral sudden deafness, including 2 cases of low-mid frequency hearing impairment, 18 cases of mid-high frequency hearing loss, 11 cases of flat-type hearing loss, and 20 cases of all frequency hearing loss. Among the 51 cases, 8 (15.69%) cases of GJB2 heterozygous variations, 1 (1.96%) case of GJB3 heterozygous variations, 5 (9.8%) cases of SLC26A4 heterozygous variations, 2 (3.92%) cases of COCH heterozygous variations, 14 (27.45%) cases of CDH23 heterozygous variations, 14 (27.45%) cases of OTOF heterozygous variations, 1 (1.96%) case of SLC17A8 heterozygous variations and 2 (3.92%) cases of KCNE1 heterozygous variations. No mtDNA gene variations were identified. CONCLUSION: SSNHL has some relationship with hereditary in Chinese population, but its complex genetic pathogenic mechanisms need further study.

Genetic Polymorphisms in Sudden Sensorineural Hearing Loss: An Update.

OBJECTIVE: To investigate the association between genetic polymorphisms and sudden sensorineural hearing loss (SSNHL). Most of the SSNHL cases still remain idiopathic, and several etiopathogenetic hypotheses, including a genetic predisposition, have been proposed. METHODS: A literature review was conducted using different databases: Medline/PubMed, EMBASE, and CINAHL, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. All databases have been searched from May 2016 to April 2020. RESULTS: Genetic susceptibility could represent a key element in the pathogenesis of SSNHL. A number of genetic polymorphisms related to (1) inner ear microvascular disease and endothelial dysfunction and (2) to inner ear oxidative stress and inflammation have been addressed in the current literature. CONCLUSIONS: The potential identification of a genetic profile related to SSNHL could provide a more accurate prognostic evidence of idiopathic SSNHL (ISSNHL), offering to the patients not only early-prevention strategies but eventually information on various inheritance modalities.

Biomarkers Suggesting Favorable Prognostic Outcomes in Sudden Sensorineural Hearing Loss.

Sudden sensorineural hearing loss (SSNHL) is a medical emergency, making detailed examination to determine possible causes and early treatment important. However, etiological examinations in SSNHL do not always reveal a cause, and several factors have been found to affect treatment outcomes. Various studies are being performed to determine the prognosis and effects of treatment in patients who experience sudden hearing loss, and to identify biomarkers associated with this condition. Embase, PubMed, and the Cochrane database were searched using the key words SSNHL, prognostic, and biomarker. This search identified 4 articles in Embase, 28 articles in PubMed, and 36 in the Cochrane database. Of these 68 articles, 3 were duplicates and 37 were unrelated to the research topic. After excluding these articles, the remaining 28 articles were reviewed. Factors associated with SSNHL were divided into six categories: metabolic, hemostatic, inflammatory, immunologic, oxidative, and other factors. The associations between these factors with the occurrence of SSNHL and with patient prognosis were analyzed. Low monocyte counts, low neutrophil/lymphocyte ratio (NLR) and monocyte/high-density lipoproteins (HDL) cholesterol ratio (MHR), and low concentrations of fibrinogen, platelet glycoprotein (GP) IIIa, and TNF-α were found to be associated with good prognosis. However, these factors alone could not completely determine the onset of and recovery from SSNHL, suggesting the need for future basic and clinical studies.

microRNAs in sudden hearing loss.

OBJECTIVES: To compare the circulating microRNA (miRNA) expression profiles between sudden sensory neural hearing loss (SSNHL) patients and age-matched normal hearing controls. STUDY DESIGN: Prospective cohort multi-center study. METHODS: Patients presenting within 28 days of onset of SSNHL were prospectively recruited along with contemporaneous age-matched controls. Pooled sera of four patient (n = 09, mean age = 53.0 years; 07, 55.0; 10, 52.9; 10, 51.6) and two control (09, 51.2 and 03, 50.0) groups were assessed using a TaqMan Low Density Array. The patients' sera were also divided into two pools, untreated (04, 57.7) and treated (32, 52.6) for additional analysis. miRNA expression level was derived from cycle threshold (Ct) values normalized to a global mean. Inter-group mean Ct differences with fold changes ≥2.0 and ≤0.5 at P < .05 were considered significant. Bioinformatic databases were used to identify putative target mRNAs or validated genes and their functional annotations. RESULTS: Thirty-six SSNHL patients (mean age 53.0 ± standard deviation (SD) 15.2 years) and 12 controls (50.9 ± 11.9) were studied. Eight miRNAs hsa-miR-590-5p/ -186-5p/ -195-5p/ -140-3p/ -128-3p/ -132-3p/ -375-3p, and -30a-3p were identified as significantly differentially expressed in SSNHL patients. Most of these miRNAs were abundantly identified in the nervous system and the putative target messenger RNAs (mRNAs) were enriched in signaling pathways such as phosphatidyl inositol 3 kinase/protein Kinase B (PI3K/Akt), Ras and mitogen-activated protein kinase (MAPK). CONCLUSION: These findings suggest the possible cellular signaling pathways that underlie the disruption of auditory signal transmission in SSNHL. LEVEL OF EVIDENCE: 2 Laryngoscope, 130:E416-E422, 2020.

Hereditary bilateral sudden sensorineural hearing loss.

OBJECTIVES: The aim of our study is to demonstrate a causal link between two distinct diagnoses, the hereditary hearing loss, and the sudden sensorineural hearing loss. BACKGROUND: Sudden sensorineural hearing loss is an emergency condition in otolaryngology and a rare diagnosis in childhood. Most often it only affects one ear and its cause remains unknown. METHODS: We present a clinical study of a 10-year-old female patient presenting with bilateral sudden sensorineural hearing loss analyzed by Sanger sequencing of the GJB2 gene. RESULTS: The subject was referred to the hospital for bilateral sudden hearing loss which developed 3 days before the admission. Audiometric testing confirmed bilateral asymmetric sensorineural hearing loss. All routine diagnostic procedures including MRI and CT imaging showed normal results. She was treated with intravenous and intratympanic corticosteroids followed by hyperbaric oxygen therapy with partial hearing recovery in one ear. DNA analysis of the GJB2 gene identified biallelic c.35delG deletion. The subject had no other affected family members and her auditory development to that time was normal. CONCLUSION: Our finding extends the knowledge on phenotype variability in GJB2 variants. We suggest considering genetic testing in pediatric cases of bilateral sudden sensorineural hearing loss (Tab. 1, Fig. 4, Ref. 24).

Nefropatía asociada a mutación del gen MYH9 / MYH9 Associated nephropathy

Las enfermedades relacionadas con mutaciones del gen MYH9 son un grupo de patologías genéticas raras. Su herencia sigue un patrón autosómico dominante en donde el gen MYH9, codifica la cadena pesada de la miosina IIA no muscular que se expresa en diferentes tejidos pero especialmente en los podocitos y en las células mesangiales. Este trastorno se caracteriza por la presencia de macrotrombocitopenia, inclusiones leucocitarias y un riesgo variable de desarrollar insuficiencia renal, hipoacusia y cataratas en edad juvenil o adulta. Describimos el caso de una mujer de 27 años, de raza caucásica, diagnosticada inicialmente de púrpura trombocitopénica idiopática. Tras una detallada historia familiar y el desarrollo de síntomas clínicos posteriores con afectación renal e hipoacusia, se le realizó un estudio genético que nos permitió el diagnóstico de nefropatía asociada a la mutación en el gen MYH9. Este caso destaca el retraso del diagnóstico y la utilidad del estudio genético en pacientes con enfermedades muy poco frecuentes. Se procede a la revisión de la enfermedad en este artículo

MYH9 related diseases are caused by mutations in the MYH9 gene and constitute a rare group of genetic entities. Its inheritance follows an autosomal dominant pattern. The MYH9 gene, encodes the nonmuscle myosin heavy chain IIA, expressed in different tissues and especially in podocytes and mesangial cells. The disorder is characterized by the presence of macrothrombocytopenia, leukocyte inclusions and a variable risk of developing renal failure, hearing loss and early-onset cataracts. We describe the case of a 27-year-old Caucasian woman, diagnosed initially with idiopathic thrombocytopenic purpura. After a detailed family history and the appearance of renal involvement and hearing loss, genetic testing allowed to make the diagnosis of nephropathy associated with MYH9 mutation. This case is an example of the delayed diagnosis of uncommon diseases and highlights the usefulness genetic testing. A review of the disease is provided

Genetic Polymorphisms and Susceptibility to Sudden Sensorineural Hearing Loss: A Systematic Review.

BACKGROUND: Recently, genetic factors have been considered as an important risk factor for sudden sensorineural hearing loss (SSNHL). Many studies analyzed the association between SSNHL and polymorphisms. However, most of them gave inconclusive results. Key Message: We performed a systematic review to find out the association between polymorphisms and susceptibility to SSNHL. Finally, 47 studies involving 5,230 SSNHL patients and 68 genes were included for analysis and discussion of results. Polymorphisms in 26 genes have been suggested to be correlated with the susceptibility to SSNHL. SUMMARY: Although a great number of studies support that polymorphisms in genes are associated with susceptibility to SSNHL, we need large multicenter studies, which evaluate multiple single nucleotide polymorphisms in SSNHL patients, to find real genetic risk factors for susceptibility to SSNHL. This is very helpful in designing more effective prevention and treatment strategies for patients with SSNHL.

MTHFR AND ApoE genetic variants association with sudden sensorineural hearing loss.

HYPOTHESIS: Although the pathogenesis of sudden sensorineural hearing loss (SSNHL) is not clear, however several causes including genetic factors seems to be implicated. We hypothesized that common genetic variants might be involved in SSNHL. BACKGROUND: SSNHL is known to be an idiopathic disease because the causative factors have not been identified. Several causes including genetic and viral infection besides immune system reaction, neurological disorders, medications, etc. have been previously reported. We examined the association between ApoE and MTHFR gene variants in SSNHL. METHODS: This study includes case-control scheme encompassing a total of 177 individuals, include patients inflicted with SSNHL and healthy subjects as control group. Genotyping of MTHFR and ApoE variants was conducted by PCR - RFLP method. RESULT: Our study showed that MTHFR rs1801133 allele frequency is significantly different between cases and controls. Also genotype distribution of ApoE was significantly different between patients and healthy controls. CONCLUSIONS: MTHFR C677T and ApoE gene variant may be associated with sudden sensorineural hearing loss in an Iranian population.

eNOS gene Glu298Asp variant confer risk in sudden sensorineural hearing loss.

BACKGROUND: Sudden sensorineural hearing loss (SSNHL) causes the loss of hearing of 30 dB or greater on at least three contiguous frequencies. It is known to be a multifactorial disease which the exact cause is unknown, rendering it as an idiopathic disorder of patients. AIMS/OBJECTIVES: This study aims to shed further light on pathogenesis of this disease by studying the association between eNOS gene Glu298Asp polymorphism and VDR gene FokI polymorphism with SSNHL in Iranian population. MATERIAL AND METHODS: This study involves a total of 77 cases and 100 controls, with patients inflicted with SSNHL categorized in case group and healthy subjects as control group. Genotyping of the VDR and eNOS genes was conducted by the polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) method. RESULTS: Our results showed a statistically significant association between genotype frequencies of eNOS gene Glu298Asp polymorphism in case group compared to healthy individuals in the control group (p = .01). Also, TT genotype was significantly the most prevalent genotype in case group in comparison to control group (TT vs GT + GG, OR = 3.5; 95% CI = 1.18-11.79). On the other hand, analysis of VDR gene FokI polymorphism frequencies showed no statistically significant association with SSNHL. CONCLUSIONS AND SIGNIFICANCE: Our findings showed a significant association between the eNOS gene Glu298Asp polymorphism and SSNHL in the Iranian population; and "TT" genotype might be considered as a risk factor for SSNHL.

Association between Uncoupling Protein 2 Gene Ala55val Polymorphism and Sudden Sensorineural Hearing Loss.

OBJECTIVES: The pathology of sudden sensorineural hearing loss, which is known as sudden deafness (SD), remains unknown. The purpose of this study was to investigate the association between mitochondrial uncoupling protein 2 (UCP2) polymorphism and SD risk. MATERIALS AND METHODS: We compared 83 patients suffering from SD and 2048 controls who participated in the Longitudinal Study of Aging at the National Institute for Longevity Sciences. Multiple logistic regression was used to calculate the odds ratios (ORs) for SD with a polymorphism of the UCP2 (rs660339) gene. RESULTS: Under the additive model of inheritance, UCP2 polymorphisms showed significant association with a SD risk. The OR was 1.468 (95% confidence interval, 1.056-2.040) with an adjustment for any past history, such as diabetes, dyslipidemia, or hypertension, and for age and sex. CONCLUSION: Our results imply that the UCP2 (rs660339) polymorphism has a significant association with the risk of developing SD.

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

Sudden sensorineural hearing loss (SSNHL) is a multifactorial disease, and its etiology remains elusive. SSNHL is possibly caused by both the environmental factors and genetic alterations. Recently, several studies suggested that inflammation may be involved in the pathogenesis of SSNHL, and certain gene polymorphisms may have correlations with SSNHL. Interleukin 6 (IL-6) functions both as a pro-inflammatory cytokine and an anti-inflammatory factor. Intercellular adhesion molecule-1 (ICAM-1) is a member of the immunoglobulin family that is also involved in inflammation response. Importantly, the IL-6 gene promoter contains a single nucleotide polymorphism (SNP), -572C/G, and ICAM-1 gene contains a SNP (A/G) in the protein-coding region, Lys (AAG)/Glu (GAG) at codon 469, known as K469E polymorphism. However, there is no study about the ICAM-1 gene polymorphism among SSNHL patients. In this study, we explored the relationship between SSNHL with IL-6 -572C/G and ICAM-1 K469E polymorphisms. We conducted a case-control study including 75 SSNHL patients and 165 healthy controls and analyzed the distribution and odds ratios of IL-6 and ICAM-1 genotypes. The frequency of the G allele at IL-6 -572C/G polymorphism was significantly higher among SSNHL patients than that among healthy individuals. In multivariate analysis, the coexistence of IL-6 -572G allele (GG/CG) and E allele (EE/KE) of ICAM-1 K469E polymorphism was significantly associated with an increased SSNHL risk (P < 0.001). In conclusion, we propose that the combination of IL-6 -572C/G and ICAM-1 K469E polymorphisms have a synergistic effect on the onset of SSNHL.

Glutathione peroxidase 3 gene polymorphisms and the risk of sudden sensorineural hearing loss.

The glutathione peroxidase 3 gene (GPX3) is reported to be a risk factor for arterial ischaemic stroke and cerebral venous thrombosis. GPX3 may be one of the aetiologies of sudden sensorineural hearing loss (SSNHL), which might be attributed to the genetic effect of GPX3 by influence reactive oxygen species (ROS). Unbalanced ROS have been associated with susceptibility to SSNHL. Therefore, we conducted a case-control study with 416 SSNHL cases and 255 controls. Five single nucleotide polymorphisms (SNPs) were selected. The genotypes were determined using TaqMan genotyping assays. Each SNP was tested using the Hardy-Weinberg equilibrium (HWE), and the genetic effects were evaluated using three inheritance models. All five SNPs were in HWE. As the result, the AG genotype of rs3805435 had an adjusted odds ratio (OR) of 0.54 (95% confidence interval = 0.37-0.79, p = 0.001) compared with the AA genotype in the SSNHL cases. The GG and AG genotypes of the SNP rs3805435 were associated with SSNHL under the dominant model (p = 0.002, OR = 0.58). In conclusion, these results suggest that GPX3 polymorphisms influence susceptibility to SSNHL in southern Taiwan.

Studying the Association between Sudden Hearing Loss and DNA N-Methyltransferase 1 (DNMT1) Genetic Polymorphism.

OBJECTIVE: The aim of the present study was to investigate whether there was any relationship between some DNA N-methyltransferase 1 (DNMT1) polymorphisms and susceptibility to idiopathic sudden sensorineural hearing loss (ISSHL) in ISSHL patients. MATERIAL AND METHODS: We investigated 90 patients diagnosed with ISSHL and a control group composed of 75 age- and gender-matched healthy individuals. DNA was extracted from the blood samples by phenol-chloroform method. Polymerase chain reaction and restriction fragment length polymorphism methods were used for the genotyping analysis of 4 regions of DNMT1. RESULTS: For rs2228612 single nucleotide polymorphism (SNP), the frequency of AA, AG, and GG genotypes were 81.4%, 9.3%, and 9.3% in controls and 82.2%, 16.7%, and 1.1% in patients, respectively. We observed a significant decrease in the frequency of GG genotype in patients with ISSHL when compared with controls (p=0.027). The frequency of GG, AG, and AA genotypes for rs2228611 SNP were 20.7%, 49.3%, and 20% in controls and 20%, 47.8%, and 32.2% in patients, respectively. There was a significantly increased frequency of the AA genotype of this SNP in the DNMT1 gene, and we found that individuals with the AA genotype had 2.47 times the risk for ISSHL development than individuals with the GG genotype (p=0.41). The GAA haplotype may constitute 2.66 times the risk for ISSHL disease (OR=2.66, 95% confidence interval: 0.28-25.03). CONCLUSION: This study's results showed that the AA genotype in rs2228611 polymorphism was a risk factor in ISSHL patients and the GG genotype could be a protective factor in rs2228612 polymorphism.

Prognostic impact of gene polymorphisms in patients with idiopathic sudden sensorineural hearing loss.

OBJECTIVE: To investigate whether genetic polymorphisms (single-nucleotide polymorphism [SNPs]) have a prognostic influence on hearing recovery after standardized corticosteroid therapy. METHODS: A total of 192 gene samples from idiopathic sudden sensorineural hearing loss (SSNHL) patients registered in the Intractable Inner Ear Disease Gene Bank were enrolled and, as the candidate genes, 16 SNPs from 13 genes were selected for this study. Fischer's exact test was used to compare allele frequencies in each SNP between the patients with good hearing recovery and patients with poor hearing recovery. RESULTS: The SNPs of the GSR gene (rs2251780 and rs3779647) and NOS3 gene (rs1799983) were associated with treatment outcome (p < .05). Furthermore, there was a marginal correlation between the SNP of the NR3C1 gene (rs4912910) and treatment outcome (p = .05). CONCLUSIONS: The results of this study indicate that the analysis of genetic factors might make it possible to predict the treatment outcome, at least in part, in patients with idiopathic SSNHL.