DNA Methylation Study in Presbycusis Patients

Abstract

ABSTRACTBackgroundPresbycusis, also known as age-related hearing loss (ARHL), is the most frequent sensory disability affecting elderly adults worldwide.ARHL is typified by a bilateral, progressive, sensorineural hearing loss that is pronounced in high frequency. Conventional factors associated with ARHL include diabetes, hypertension, and family history of hereditary hearing loss. The severity of hearing impairment varies between individuals. The accurate causative molecular pathogenesis for ARHL is unknown, therefore the investigation of the underlying pathogenic mechanisms involved in ARHL is imperative for the development of effective therapeutic approaches. Epigenetics is the study of phenotypic changes caused by modification of genetic expression rather than alteration of DNA sequence. It is hypothesized that ARHL could result from unclarified epigenetic susceptibility, nevertheless, there is a shortage of information on the exact contribution of epigenetic modifications to ARHL. Here we present an investigation on the involvement of DNA methylation with Age-related hearing loss.ResultsIn the present study the Illumina Infinium® Methylation EPIC Beadchip has been used to identify regions with aberrant levels of methylation across genomes from ARHL patients. Hearing measurements were used to determine the audioprofiles. Clinical, audiometric patterns, DNA testing, and methylation pattern screening were undertaken. Our results demonstrate a strong correlation between patients’ hearing measurements and CpG sites methylation inESPNandTNFRSF25. A Methylation Polymerase chain reaction (PCR) assay was used to confirm methylation levels at specific gene locus in ARHL patients.ConclusionAberrant DNA methylation and its impact on gene expression have been implicated in many biological processes. By interrogating methylation status across the genome at single-nucleotide resolution of hearing loss patients, our study can help establish the association between audiometric patterns and methylation status in age-related hearing loss patients.