Whole-Genome DNA Methylation Analysis in Age-Related Hearing Loss

Area of Science:

• Genetics
• Epigenetics
• Otolaryngology

Background:

• Age-related hearing loss (ARHL), or presbycusis, is a widespread sensory disability in older adults.
• ARHL is characterized by progressive, bilateral, sensorineural hearing loss, often more severe at higher frequencies.
• The precise molecular causes of ARHL remain unknown, necessitating research into underlying pathogenic mechanisms.

Purpose of the Study:

• To investigate the role of DNA methylation in the pathogenesis of age-related hearing loss.
• To identify specific DNA methylation patterns associated with ARHL.
• To explore potential epigenetic susceptibility factors contributing to hearing impairment.

Main Methods:

• Clinical, audiometric, and DNA testing were performed on ARHL patients and control subjects.
• High-throughput screening identified methylation patterns across the genome.
• Methylation-specific PCR assays confirmed methylation levels at specific gene loci.

Main Results:

• A significant correlation was found between hearing measurements and methylation at CpG sites cg1140494 (ESPN) and cg27224823 (TNFRSF25).
• 136 differentially methylated CpGs were identified, common to both high and low audiometric frequencies in patients.
• CpG sites in candidate hearing loss genes (KCNQ1, TMEM43, GSTM1, TCF25, GSR) showed higher methylation in ARHL patients compared to controls.

Conclusions:

• Altered DNA methylation impacts gene expression and is implicated in various biological processes.
• This study establishes an association between audiometric patterns and DNA methylation status in ARHL.
• Findings provide new avenues for identifying candidate genes and understanding the molecular basis of hearing loss.