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Screening of noise-induced hearing loss (NIHL)-associated SNPs and the assessment of its genetic susceptibility.

ABSTRACT: BACKGROUND:The aim of this study was to screen for noise-induced hearing loss (NIHL)-associated single nucleotide polymorphisms (SNPs) and to construct genetic risk prediction models for NIHL in a Chinese population. METHODS:Four hundred seventy-six subjects with NIHL and 476 matched controls were recruited from a cross-sectional survey on NIHL in China. A total of 83 candidate SNPs were genotyped using nanofluidic dynamic arrays on a Fluidigm platform. NIHL-associated SNPs were screened with a multiple logistic model, and a genetic risk model was constructed based on the genetic risk score (GRS). The results were validated using a prospective cohort population. RESULTS:Seven SNPs in the CDH23, PCDH15, EYA4, MYO1A, KCNMA1, and OTOG genes were significantly (P??0.05 and P?

SUBMITTER: Zhang X

PROVIDER: S-EPMC6449917 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Screening of noise-induced hearing loss (NIHL)-associated SNPs and the assessment of its genetic susceptibility.

Zhang Xuhui X Ni Yaqin Y Liu Yi Y Zhang Lei L Zhang Meibian M Fang Xinyan X Yang Zhangping Z Wang Qiang Q Li Hao H Xia Yuyong Y Zhu Yimin Y

Environmental health : a global access science source 20190404 1

<h4>Background</h4>The aim of this study was to screen for noise-induced hearing loss (NIHL)-associated single nucleotide polymorphisms (SNPs) and to construct genetic risk prediction models for NIHL in a Chinese population.<h4>Methods</h4>Four hundred seventy-six subjects with NIHL and 476 matched controls were recruited from a cross-sectional survey on NIHL in China. A total of 83 candidate SNPs were genotyped using nanofluidic dynamic arrays on a Fluidigm platform. NIHL-associated SNPs were s ...[more]

PMID: 30947719

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Project description:BACKGROUND:Noise-induced hearing loss (NIHL) is a complex disease caused by environmental and genetic risk factors. This study was to explore the association of noise kurtosis, triphosphopyridine nucleotide oxidase 3 (NOX3) and lifestyles with NIHL. METHODS:This case-control study included 307 patients with NIHL and 307 matched control individuals from Zhejiang province of China. General characteristics, noise exposure data, the exfoliated cells of the oral mucosa, and lifestyle details of individuals were collected. The kompetitive allele specific polymerase chain reaction (KASP) method was used to analyze the genotypes of three single nucleotide polymorphisms (SNPs) of NOX3. RESULTS:People who exposed to complex noise had a higher risk of NIHL than those exposed to steady noise (adjusted: OR = 1.806, P = 0.002). The GT genotype of additive model and TT + GT genotype of dominant model in NOX3 rs12195525 decreased the risk of NIHL (adjusted: OR = 0.618, P = 0.043; OR = 0.622, P = 0.036). Smoking and exposure to high video volume increased the risk of NIHL (adjusted: OR = 1.486, P = 0.038; OR = 1.611, P = 0.014). Oppositely, regular physical exercise decreased the risk of NIHL (adjusted: OR = 0.598, P = 0.004). A positive interaction was found between complex noise and lifestyles including high video volume exposure and no physical exercise in the additive models (RERI = 1.088, P < 0.001; RERI = 1.054, P = 0.024). A positive interaction was also found between NOX3 rs12195525 GG genotype and lifestyles including smoking and high video volume exposure in the additive models (RERI = 1.042, P = 0.005; RERI = 0.774, P = 0.044). CONCLUSIONS:Noise temporal structure, NOX3 rs12195525 polymorphism, and the three lifestyles of smoking, video volume, and physical exercise were related to the NIHL. There were the interactions between noise temporal structure and the lifestyle of video volume or physical exercise, as well as between NOX3 and the lifestyle of smoking or video volume. These results provide a theoretical basis for the prevention and genetic testing of NIHL.

Project description:Noise-induced hearing loss (NIHL) is a prevalent form of adult hearing impairment, characterized by oxidative damage to auditory sensory hair cells. Although certain dihydropyridines, the L-type calcium channel blockers, exhibit protective properties against such damage, the ability of third-generation dihydropryidines like lercanidipine to mitigate NIHL remains unclear.We utilized glucose oxidase (GO)-treated OC1 cell lines and cochlear explants to evaluate the protective influence of lercanidipine on hair cells. To further investigate its effectiveness, we exposed noise-stimulated mice in vivo and analyzed their hearing thresholds. Additionally, we assessed the antioxidative capabilities of lercanidipine by examining oxidation-related enzyme expression and levels of oxidative stress markers, including 3-nitrotyrosine (3NT) and 4-hydroxynonenal (4HNE). Our findings demonstrate that lercanidipine significantly reduces the adverse impacts of GO on both OC-1 cell viability (0.3 to 2.5 µM) and outer hair cell (OHC) survival in basal turn cochlear explants (7 µM). These results are associated with increased mRNA expression of antioxidant enzyme genes (HO-1, SOD1/2, and Txnrd1), along with decreased expression of oxidase genes (COX-2, iNOS). Crucially, lercanidipine administration prior to, and following, noise exposure effectively ameliorates NIHL, as evidenced by lowered hearing thresholds and preserved OHC populations in the basal turn, 14 days post-noise stimulation at 110 dB SPL. Moreover, our observations indicate that lercanidipine's antioxidative action persists even three days after simultaneous drug and noise treatments, based on 3-nitrotyrosine and 4-hydroxynonenal immunostaining in the basal turn. Based on these findings, we propose that lercanidipine has the capacity to alleviate NIHL and safeguard OHC survival in the basal turn, potentially via its antioxidative mechanism. These results suggest that lercanidipine holds promise as a clinically viable option for preventing NIHL in affected individuals.

Dataset Information

Screening of noise-induced hearing loss (NIHL)-associated SNPs and the assessment of its genetic susceptibility.

Publications

Screening of noise-induced hearing loss (NIHL)-associated SNPs and the assessment of its genetic susceptibility.

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