<i>eNOS</i> gene Glu298Asp variant confer risk in sudden sensorineural hearing loss

Yazdani, Nasrin; Hamidi, Armita Kakavand; Soroush, Negin; Jalili, Neda; Vahidi, Aida; Ahrabi, Nakisa Zarabi; Tajdini, Ardavan; Amoli, Mahsa M.

doi:10.1080/00016489.2018.1497806

Cited by 7 publications

(7 citation statements)

References 20 publications

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“…Therefore, inhibition of NOS3 can reduce the synthesis of NO to protect hearing. Moreover, eNOS3 gene evidently participates in microvascular damage in sudden sensorineural hearing loss patients [39]. The survival of inner cells is associated with blood ow and vascular lesions, and activation of the ROS/PI3K/AKT/eNOS signaling pathway at the early stage confers protection against apoptosis due to high glucose levels in vascular endothelial cells [40].…”

Section: Discussionmentioning

confidence: 99%

Exploring the Pharmacological Mechanisms of Ginkgo biloba Extract in the Treatment of Sensorineural Hearing Loss

Qiu

Wang

et al. 2023

Preprint

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Backgrounds: Anincreasing people are suffering from sensorineural hearing loss (SNHL) and facing great psychological and physical stress. Although the extract of extract of Ginkgo biloba (EGb) has been widely used to treat SNHL for many years, underlying pharmacological mechanisms remain unclear. Methods: Active ingredients of EGb and compounds targets were retrieved from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). SNHL-related genes were obtained from GeneCards. Venny 2.1 was used to select common targets between active ingredients of EGb and SNHL, and Gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed. Cytoscape was used to construct a network map to assess the relationship between active ingredients, interacting targets, and signaling pathways, and Chem3D, AutoDock Tools, and PyMol were employed to perform molecular docking between active ingredients and hub genes. Besides, House Ear Institute-Organ of Corti 1 (HEI-OC1) cells were treated with cisplatin and EGb to verify target genes by quantitative Real-time PCR (q-PCR). Results: Venny diagram showing that SNHL and EGb had a total of 64 intersecting targets (core targets). The results of GO and KEGG analysis indicated that 64 core targets were involved in regulating of biological process, stabilization of cell membranes and organelles, protein binding, and diverse signaling pathways. According to the cytoscape and PPI network analyses, three genes (GSK3B, NOS3 and AKT1) and nine kinds of corresponding ingredients (kaempferol, quercetin, sesamin, luteolin, isorhamnetin, isogoycyrol, laricitrin, syringetin and chryseriol) were picked. Molecular docking demonstrates protein binding models for intersection genes and effective ingredients. Eventually, the results of q-PCR experiments further revealed that GSK3B, NOS3 and AKT1 genes exerted their functions in treatment of SNHL by EGb. Conclusions: Our findings indicate the mechanisms of action of EGb in treating SNHL. There are five active components, including luteolin, quercetin, isorhamnetin, kaempferol, and sesamin. Those ingredients exert their effects through regulating three genes (GSK3B, NOS3 and AKT1), which are involved in the PI3K-Akt signaling pathway.

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Section: Discussionmentioning

confidence: 99%

Exploring the Pharmacological Mechanisms of Ginkgo biloba Extract in the Treatment of Sensorineural Hearing Loss

Qiu

Wang

et al. 2023

Preprint

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“…28 Data in the current literature show that several genetic polymorphisms correlated with oxidative stress, inflammation, thrombosis, and blood vessel permeability are associated to SSNHL predisposition and development. 10,12,20,24,28,36,37,40,41 On the basis of this evidence, it could be hypothesized that genetic factors could play a role in maintaining the delicate balance between ROS and antioxidants, pro-inflammatory and anti-inflammatory factors, proaggregants, and antiaggregants; since the balance among these factors is important for the inner ear homeostasis, their disruption could be a factor contributing to the ISSNHL onset. Furthermore, a possible link between SSNHL and major cardiovascular diseases, such as stroke and myocardial infarction, has been previously highlighted.…”

Section: Discussionmentioning

confidence: 99%

“…Endothelial nitric oxide synthase (eNOS) produces nitric oxide (NO) inducing a vasodilation of the smooth muscle cells; the eNOS p.Glu298Asp single-nucleotide polymorphism is correlated to cardiovascular diseases. 22,23 Yazdani et al 24 found a significant association between eNOS and SSNHL in a casecontrol study, suggesting that NO plays a crucial role in cochlear neurotoxicity.…”

Section: Genetic Polymorphisms and Inner Ear Microvascular Disease And/or Endothelial Dysfunctionmentioning

confidence: 99%

Genetic Polymorphisms in Sudden Sensorineural Hearing Loss: An Update

et al. 2020

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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.

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“…The study subjects were categorized into two groups according to the cut-off level of dyslipidemia for each lipid component recommended by the Korean society of lipid and atherosclerosis [ 15 ]: TC ≥200 mg/dL, TG ≥150 mg/dL, HDL-C for male ≤40 mg/dL and for female ≤50 mg/dL, and LDL-C ≥130 mg/dL. To investigate the association of serum lipid levels and HL, study subjects were classified into four groups according to the quartile distribution of each lipid profile.…”

Section: Methodsmentioning

confidence: 99%

Association between Serum Lipid Levels and Sensorineural Hearing Loss in Korean Adult Population

et al. 2022

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Background: Hearing loss (HL) has been suggested to be associated with impaired microcirculation of the inner ear. This cross-sectional study aimed to evaluate an association between HL and serum lipid levels.Methods: The study comprised 10,356 Korean adults who participated in the fifth Korea National Health and Nutrition Examination Survey (2010–2012). We defined HL as the average hearing thresholds exceeding 25 dB at predetermined frequency levels by pure tone audiometry. Serum lipid levels were measured using an enzymatic assay. The associations between lipid levels and HL were evaluated using a multiple logistic regression model after adjusting for covariates including age, sex, hypertension, diabetes, smoking status, alcohol, physical activity, educational level, household income, and noise exposure. Stratified analyses were performed to examine the effect of the covariates on the association between lipid levels and HL.Results: The high-density lipoprotein cholesterol (HDL-C) level was inversely associated with high-frequency (HF)-HL, with an odds ratio (95% confidence interval) of 0.78 (0.64–0.96) for 1-mmol/L increase in the HDL-C level. Neither the triglyceride nor the low-density lipoprotein cholesterol level was associated with HF-HL. For low-frequency HL, association with any of the serum lipid components was absent. A stratified analysis showed that the inverse association between HDL-C levels and HF-HL was evident (P trend <0.05) in some subjects with specific characteristics such as older age (≥65 years), female sex, non-hypertensive state, and non-regular physical activity. However, a significant interaction between HDL-C levels and all of the stratified variables was absent (P for interaction >0.05).Conclusion: The HDL-C level has a linear inverse association with the risk of HF-HL. Given the known protective role of HDL-C against atherosclerotic changes, this finding seems to support the concept of impaired microcirculation in the inner ear as a mechanism for HF-HL.

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eNOS gene Glu298Asp variant confer risk in sudden sensorineural hearing loss

Cited by 7 publications

References 20 publications

Exploring the Pharmacological Mechanisms of Ginkgo biloba Extract in the Treatment of Sensorineural Hearing Loss

Exploring the Pharmacological Mechanisms of Ginkgo biloba Extract in the Treatment of Sensorineural Hearing Loss

Genetic Polymorphisms in Sudden Sensorineural Hearing Loss: An Update

Association between Serum Lipid Levels and Sensorineural Hearing Loss in Korean Adult Population

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