Abstract
BackgroundNoise induced hearing loss (NIHL) is a polygenic disease involving both genetic and environmental factors, and is one of the most important occupational health hazards worldwide. To date, the influence of Notch1 variants on the risk to develop NIHL has not been illuminated. This study was conducted to explore the effects of Notch1 polymorphisms on individual susceptibility to NIHL.MethodsA total of 2689 industrial workers from one textile factory in east China were recruited to participate in the current study. Venous blood was collected, basic clinical data was obtained by questionnaires and pure-tone audiometry (PTA) tests were conducted by specialist physicians. Next we performed genotyping of three selected SNPs (rs3124594, rs3124599 and rs3124603) in the Notch1 gene in 535 NIHL patients and 535 controls. Subsequently, the main effects of the genotypes and their interactions were evaluated.ResultsOur results revealed that individuals with a GG of rs3124594, TT of rs3124603 (OR = 4.70 and 1.59 respectively) and the haplotype AAC (rs3124594-rs3124599-rs3124603) (OR = 14.95) were associated with an increased risk of NIHL in our study cohort. Stratified analysis showed that an increased NIHL risk was found in individuals exposed to work related noise for ≤16 years that also had the rs3124594 GG or rs3124603 CT/TT genotype with an OR of 4.20 and 1.73 respectively. Multifactor dimensionality reduction analysis indicated that rs3124594, rs3124599 and rs3124603 interacted with each other and were related to an increased risk to develop NIHL (OR = 3.60).ConclusionsThe genetic polymorphisms rs3124594 and rs3124603 within the Notch1 gene are associated with an increased risk of NIHL in a Chinese population and could potentially be used as biomarkers for NIHL in noise exposed workers.
Highlights
Noise induced hearing loss (NIHL) is a polygenic disease involving both genetic and environmental factors, and is one of the most important occupational health hazards worldwide
The Notch receptor Notch1 is expressed in the developing cochlea, including the presumptive sensory epithelium, while the Notch ligands Dll1 and Jag2 are expressed in the developing hair cells (HC) [14,15,16]
We found that the haplotype AAC in the Notch1 gene was associated with an increased risk of NIHL (OR = 14.95), whereas the haplotype GGC and GGT were associated with a decreased risk for NIHL (OR = 0.11 and 0.02) compared with GAC
Summary
Noise induced hearing loss (NIHL) is a polygenic disease involving both genetic and environmental factors, and is one of the most important occupational health hazards worldwide. Loss of either Notch ligand Dll or Jag in the developing cochlea was found to result in the formation of extra rows of hair cells [17]. The loss of responsiveness to inhibition of the Notch pathway was partly induced by the downregulation of Notch receptors and ligands. This downregulation still persisted in the adult animals, even under conditions of noise damage [20]. Notch signaling may play a vital role both in maintaining the homeostasis of the cochlear sensory epithelium and the mitotic regeneration of hair cells
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
