Polymorphisms in the FAS gene are associated with susceptibility to noise-induced hearing loss.

Abstract

This study investigated the relationship between genetic polymorphisms in the FAS gene and noise-induced hearing loss (NIHL) risk among Chinese workers exposed to occupational noise, and the molecular mechanism of NIHL caused by noise. In this case-control study, 692 NIHL workers and 650 controls were selected for genotyping of four single nucleotide polymorphisms (SNPs) of the FAS gene. Logistic regression was used to calculate the odds ratio (OR) and 95% confidence interval (CI) of the association of these genetic polymorphisms and NIHL. At the same time, a noise-exposed rat model was constructed to further clarify the effect of noise exposure on fas gene expression and the pathogenic mechanism of NIHL. Two polymorphisms, rs1468063 and rs2862833, were associated with NIHL in the case-control study. Individuals with the rs1468063-TT or rs2862833-AA genotypes had decreased NIHL risk (p < 0.01, p = 0.02, respectively). Compared with the control group, the hearing threshold of the case group of rats increased, while serum MDA, urine 8-OHdG, and fas gene expression increased, but let-7e expression decreased. Genetic polymorphisms in the FAS gene are related to the risk of NIHL in the Chinese population. Noise can cause a large amount of reactive oxygen species (ROS) in the cochlea tissue and blood, which lead to oxidative stress, lipid peroxidation, and DNA damage, further activating the FAS gene, and ultimately leading to hearing loss.