Key Laboratory of Environmental Medicine Engineering of Ministry of Education, School of Public Health, Southeast University, Nanjing, Jiangsu, China.
Jiangsu Provincial Center for Disease Prevention and Control, Nanjing, Jiangsu, China.
Environ Sci Pollut Res Int. 2021 May;28(17):21754-21765. doi: 10.1007/s11356-020-12028-9. Epub 2021 Jan 7.
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.
本研究旨在探讨中国职业噪声暴露工人中 FAS 基因遗传多态性与噪声性听力损失（NIHL）风险之间的关系，以及噪声引起的 NIHL 的分子机制。在这项病例对照研究中，选择了 692 名 NIHL 工人和 650 名对照进行 FAS 基因四个单核苷酸多态性（SNP）的基因分型。采用 logistic 回归计算这些遗传多态性与 NIHL 关联的比值比（OR）和 95%置信区间（CI）。同时，构建了噪声暴露大鼠模型，以进一步阐明噪声暴露对 fas 基因表达的影响及 NIHL 的致病机制。在病例对照研究中，两个多态性 rs1468063 和 rs2862833 与 NIHL 相关。与 TT 基因型或 AA 基因型个体相比，rs1468063-TT 或 rs2862833-AA 基因型个体的 NIHL 风险降低（p<0.01，p=0.02）。与对照组相比，大鼠病例组的听力阈值升高，而血清 MDA、尿 8-OHdG 和 fas 基因表达增加，let-7e 表达减少。FAS 基因的遗传多态性与中国人群中 NIHL 的风险相关。噪声可引起耳蜗组织和血液中大量活性氧（ROS），导致氧化应激、脂质过氧化和 DNA 损伤，进一步激活 FAS 基因，最终导致听力损失。
