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

Area of Science:

• Genetics
• Occupational Health
• Audiology

Background:

• Noise-induced hearing loss (NIHL) is a prevalent global occupational health problem.
• Identifying genetic predispositions is crucial for understanding NIHL susceptibility.
• Nucleolin is implicated in cellular senescence, apoptosis, and stress response pathways.

Purpose of the Study:

• To identify genetic variants associated with hearing threshold shift in young males exposed to occupational impulse noise.
• To investigate the role of the nucleolin gene in NIHL susceptibility.
• To explore the functional significance of nucleolin in cochlear sensory cells under stress.

Main Methods:

• Genome-wide association study (GWAS) in young males exposed to occupational impulse noise.
• Statistical analysis of single-nucleotide polymorphisms (SNPs) and hearing threshold shift.
• In vitro studies using cochlear sensory cells (HEI-OC1) to assess nucleolin function under oxidative stress.

Main Results:

• A significant association was found between SNP rs7598759 in the nucleolin gene and NIHL (p < 5 x 10(-7)).
• Nucleolin down-regulation in cochlear cells increased sensitivity to ototoxic cisplatin, suggesting a protective role.
• Additional suggestive SNP associations were identified, including those in known NIHL-related genes and novel candidate genes.

Conclusions:

• The nucleolin gene, particularly SNP rs7598759, is a potential candidate associated with NIHL susceptibility.
• Nucleolin may play a protective role against noise-induced ototoxicity and apoptosis in cochlear sensory cells.
• GWAS combined with in vitro functional studies provides valuable insights into the genetic basis of NIHL.