Objective: To investigate the relationship between rs1053005 of signal conversion and transcription activator 3 (STAT3) and miR-452-3p, and the association between STAT3 gene polymorphism and noise-induced hearing loss (NIHL) . Methods: In December 2017, 1220 workers were selected from an automobile manufacturing factory, an energy company and a chemical fiber factory in Jiangsu Province who had occupational noise exposure and working age of more than 3 years. The workers with the mean hearing threshold of ≥26 dB (A) of the two ear high frequency (3000, 4000 and 6000 Hz) were defined as case group (n=609) , and the rest were control group (n=611) . Five single nucleotide polymorphism (SNP) sites of STAT3 (rs4796793, rs1053023, rs1053005, rs1053004 and rs3744483) were selected to explore the association between STAT3 gene polymorphism and NIHL by analyzing the points. The double luciferase reporter gene verified whether miR-452-3p was targeted to bind STAT3, and overexpressed miR-452-3p in HEI-OC1 cells to explore the mechanism of STAT3 expression regulation. Results: There was no significant difference in gender, age, smoking and drinking between the two groups (P>0.05) . Compared with the control group[ (15.58±4.76) dB], the mean hearing threshold of the case group [ (37.50±12.39) dB] was higher, and the difference were statistically significant (P<0.05) . Compared with the control group, the C alleles of rs1053023 and rs1053005 were higher in the case group (OR=1.367, 1.370, P<0.05) . The risk of NIHL in men with TC/CC genotype were 1.545 and 1.531 times higher than that in men with TT genotype (P<0.05) . Compared with the control group, the mRNA expression of STAT3 in the case group was significantly increased (P<0.05) . The STAT3 mRNA expression of miR-452-3p group cells was significantly decreased (P<0.05) . Conclusion: The rs1053023 and rs1053005 polymorphism of STAT3 are related to NIHL. The C alleles of rs1053023 and rs1053005 may be biomarkers of workers exposed to noise.
目的： 探讨信号转换和转录激活因子3（STAT3）的rs1053005位点与miR-452-3p靶向结合及STAT3的基因多态性与噪声性听力损失（NIHL）的关联。 方法： 于2017年12月，选择江苏省2017年参加职业健康体检的某汽车制造工厂、某能源公司以及某化纤工厂的有职业性噪声接触且工龄≥3年的1 220名在岗工人作为研究对象。将双耳高频（3 000、4 000和6 000 Hz）平均听力阈值≥26 dB（A）的工人作为病例组（609人），其余为对照组（611人）。选取STAT3的rs4796793、rs1053023、rs1053005、rs1053004和rs3744483位点，探索STAT3基因多态性与NIHL的关联。双荧光素酶报告基因验证miR-452-3p是否靶向结合STAT3，并在HEI-OC1细胞中过表达miR-452-3p探索STAT3的表达调节机制。 结果： 病例组和对照组工人性别、年龄、吸烟情况、饮酒情况差异均无统计学意义（P>0.05）。与对照组[（15.58±4.76）dB]比较，病例组工人的听力阈值[（37.50±12.39）dB]较高，差异有统计学意义（P<0.05）。与对照组比较，病例组工人rs1053023和rs1053005位点的C等位基因较高，差异均有统计学意义（OR(校正)=1.367、1.370，P<0.05）。男性携带TC/CC联合基因型患NIHL风险分别是携带TT基因型的1.545和1.531倍（P<0.05）。与对照组比较，病例组工人STAT3的mRNA表达量明显升高，差异有统计学意义（P<0.05）。miR-452-3p组细胞STAT3的mRNA表达量明显降低，差异有统计学意义（P<0.05）。 结论： STAT3的rs1053023和rs1053005位点的基因多态性与NIHL存在关联，rs1053023和rs1053005位点的C等位基因可能是噪声接触工人的生物标记。.
Keywords: Genes; Hearing loss; Noise; Noise-induced hearing loss; Signal conversion and transcription activator 3; Single nucleotide polymorphism.