Dataset Information

Genetic Polymorphisms Associated with Hearing Threshold Shift in Subjects during First Encounter with Occupational Impulse Noise.

ABSTRACT: Noise-induced hearing loss (NIHL) is the most significant occupational health issue worldwide. We conducted a genome-wide association study to identify single-nucleotide polymorphisms (SNPs) associated with hearing threshold shift in young males undergoing their first encounter with occupational impulse noise. We report a significant association of SNP rs7598759 (p < 5 x 10(-7); p = 0.01 after permutation and correction; Odds Ratio = 12.75) in the gene coding for nucleolin, a multifunctional phosphoprotein involved in the control of senescence and protection against apoptosis. Interestingly, nucleolin has been shown to mediate the anti-apoptotic effect of HSP70, a protein found to prevent ototoxicity and whose polymorphisms have been associated with susceptibility to NIHL. Increase in nucleolin expression has also been associated with the prevention of apoptosis in cells undergoing oxidative stress, a well-known metabolic sequela of noise exposure. To assess the potential role of nucleolin in hearing loss, we tested down-regulation of nucleolin in cochlear sensory cells HEI-OC1 under oxidative stress conditions and report increased sensitivity to cisplatin, a chemotherapeutic drug with ototoxic side effects. Additional SNPs were found with suggestive association (p < 5 x 10(-4)), of which 7 SNPs were located in genes previously reported to be related to NIHL and 43 of them were observed in 36 other genes previously not reported to be associated with NIHL. Taken together, our GWAS data and in vitro studies reported herein suggest that nucleolin is a potential candidate associated with NIHL in this population.

SUBMITTER: Grondin Y

PROVIDER: S-EPMC4488244 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Genetic Polymorphisms Associated with Hearing Threshold Shift in Subjects during First Encounter with Occupational Impulse Noise.

Grondin Yohann Y Bortoni Magda E ME Sepulveda Rosalinda R Ghelfi Elisa E Bartos Adam A Cotanche Douglas D Clifford Royce E RE Rogers Rick A RA

PloS one 20150629 6

Noise-induced hearing loss (NIHL) is the most significant occupational health issue worldwide. We conducted a genome-wide association study to identify single-nucleotide polymorphisms (SNPs) associated with hearing threshold shift in young males undergoing their first encounter with occupational impulse noise. We report a significant association of SNP rs7598759 (p < 5 x 10(-7); p = 0.01 after permutation and correction; Odds Ratio = 12.75) in the gene coding for nucleolin, a multifunctional pho ...[more]

PMID: 26121033

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Project description:ObjectivesOne of the challenges for evaluating new otoprotective agents for potential benefit in human populations is the availability of an established clinical paradigm with real-world relevance. These studies were explicitly designed to develop a real-world digital music exposure that reliably induces temporary threshold shift (TTS) in normal-hearing human subjects.DesignThirty-three subjects participated in studies that measured effects of digital music player use on hearing. Subjects selected either rock or pop music, which was then presented at 93 to 95 (n = 10), 98 to 100 (n = 11), or 100 to 102 (n = 12) dBA in-ear exposure level for a period of 4 hr. Audiograms and distortion product otoacoustic emissions (DPOAEs) were measured before and after music exposure. Postmusic tests were initiated 15 min, 1 hr 15 min, 2 hr 15 min, and 3 hr 15 min after the exposure ended. Additional tests were conducted the following day and 1 week later.ResultsChanges in thresholds after the lowest-level exposure were difficult to distinguish from test-retest variability; however, TTS was reliably detected after higher levels of sound exposure. Changes in audiometric thresholds had a "notch" configuration, with the largest changes observed at 4 kHz (mean = 6.3 ± 3.9 dB; range = 0-14 dB). Recovery was largely complete within the first 4 hr postexposure, and all subjects showed complete recovery of both thresholds and DPOAE measures when tested 1 week postexposure.ConclusionsThese data provide insight into the variability of TTS induced by music-player use in a healthy, normal-hearing, young adult population, with music playlist, level, and duration carefully controlled. These data confirm the likelihood of temporary changes in auditory function after digital music-player use. Such data are essential for the development of a human clinical trial protocol that provides a highly powered design for evaluating novel therapeutics in human clinical trials. Care must be taken to fully inform potential subjects in future TTS studies, including protective agent evaluations, that some noise exposures have resulted in neural degeneration in animal models, even when both audiometric thresholds and DPOAE levels returned to pre-exposure values.

Project description:ObjectiveMost of the Chinese occupational population are becoming at risk of noise-induced hearing loss (NIHL). However, there is a limited number of literature reviews on occupational NIHL in China. This study aimed to analyse the prevalence and characteristics of occupational NIHL in the Chinese population using data from relevant studies.DesignSystematic review and meta-analysis.MethodsFrom December 2019 to February 2020, we searched the literature through databases, including Web of Science, PubMed, MEDLINE, Scopus, the China National Knowledge Internet, Chinese Sci-Tech Journal Database (weip.com), WanFang Database and China United Library Database, for studies on NIHL in China published in 1993-2019 and analysed the correlation between NIHL and occupational exposure to noise, including exposure to complex noise and coexposure to noise and chemicals.ResultsA total of 71 865 workers aged 33.5±8.7 years were occupationally exposed to 98.6±7.2 dB(A) (A-weighted decibels) noise for a duration of 9.9±8.4 years in the transportation, mining and typical manufacturing industries. The prevalence of occupational NIHL in China was 21.3%, of which 30.2% was related to high-frequency NIHL (HFNIHL), 9.0% to speech-frequency NIHL and 5.8% to noise-induced deafness. Among manufacturing workers, complex noise contributed to greater HFNIHL than Gaussian noise (overall weighted OR (OR)=1.95). Coexposure to noise and chemicals such as organic solvents, welding fumes, carbon monoxide and hydrogen sulfide led to greater HFNIHL than noise exposure alone (overall weighted OR=2.36). Male workers were more likely to experience HFNIHL than female workers (overall weighted OR=2.26). Age, noise level and exposure duration were also risk factors for HFNIHL (overall weighted OR=1.35, 5.63 and 1.75, respectively).ConclusionsThe high prevalence of occupational NIHL in China was related to the wide distribution of noise in different industries as well as high-level and long-term noise exposure. The prevalence was further aggravated by exposure to complex noise or coexposure to noise and specific chemicals. Additional efforts are needed to reduce occupational noise exposure in China.

Project description:BackgroundNoise-induced hearing loss (NIHL) is a complex disease induced by a combination of genetic and environmental factors. Paraoxonase2 (PON2) gene involved in the regulation of reactive oxygen species, and affecting the vulnerability of cochlea to NIHL, and ATPase, calcium-transporting, plasma membrane 2 (ATP2B2) gene which encodes plasma membrane calcium-transporting ATPase isoform 2 (PMCA2) are the candidate genes relating to the attack of NIHL. In this study, we investigated whether ATP2B2 and PON2 polymorphisms were associated with NIHL in Chinese of Han nationality population.MethodsWe performed a case-control study between six single nucleotide polymorphisms (SNPs) (rs1719571, rs3209637 and rs4327369 within ATP2B2, rs12026, rs7785846 and rs12704796 within PON2) and NIHL in 454 subjects. All the SNPs were genotypes, using the TaqMan MGB probe assay. Odds ratios (ORs) were calculated with 95% confidence intervals (95% CIs) with logistic regression analysis to test the level of association for SNPs.ResultsIn our study, 221 subjects with hearing loss and 233 subjects without hearing loss were recruited. The frequencies of the CG and CG + GG genotype of rs12026 (PON2) conferred risk factors for NIHL with adjusted OR values of 2.62 (95% CI, 1.69-4.06) and 2.48 (95% CI, 1.63-3.78), respectively. This kind of significance was also found at locus rs7785846, where genotypes CT and CT + TT were the risk types, with adjusted ORs of 2.52 (95% CI, 1.62-3.93) and 2.35 (95% CI, 1.54-3.58), respectively. We performed stratified analysis per noise exposure level, when it came to rs7785846 and rs12026 in the >92 dB(A) noise exposure group, the subjects who carried heterozygote were of significantly (P<0.01) higher susceptibility to NIHL than homozygote carriers. By contrast, no significantly higher risk was found for any rs12704796 genotypes or any genotypes in ATP2B2 (P>0.05), which may suggest that these SNPs did not have significant effects on noise susceptibility across noise exposure.ConclusionsOur research suggested that PON2 might play a role in the etiology of NIHL in Chinese of Han nationality population.

Dataset Information

Genetic Polymorphisms Associated with Hearing Threshold Shift in Subjects during First Encounter with Occupational Impulse Noise.

Publications

Genetic Polymorphisms Associated with Hearing Threshold Shift in Subjects during First Encounter with Occupational Impulse Noise.

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