Objective: To explore the effect of gene polymorphism on workers suffering from noise induced hearing loss (NIHL) . Methods: In May 2019, a case-control study was conducted to select noise exposed workers in five factories in Zhejiang Province from 2017 to 2018. The average hearing threshold of binaural high frequency (3, 4, 6 kHz) was >25 dB (A) as the NIHL group, and the hearing threshold of any language frequency (0.5, 1, 2 kHz) was ≤25 dB (A) as the non NIHL group, with 307 people in each group. The general demographic data, occupational history, pure tone audiometry results and oral swab mucosal samples of noise exposed workers were collected, and the DNA of oral mucosal cells was extracted. The relationship between genetic risk score (GRS) and NIHL was analyzed, single nucleotide polymorphisms (SNP) were genotyped, the relationship between genotype and NIHL was analyzed by logistic regression, and the relationship between haplotype and NIHL was analyzed by R language. Results: After adjusting for gender, age, education and working years, the risk of NIHL among workers carrying cysteine-aspartic acid protease 3 gene (CASP3) rs1049216 recessive model GG genotype, rs6948 recessive model TT genotype, NADPH oxidase 3 gene (NOX3) rs12195525 additive model GT genotype and dominant model TT+GT genotype decreased (P<0.05) , the risk of disease was higher in workers with AA genotype carrying cysteine-aspartic acid protease 7 gene (CASP7) rs12415607 additive model (P<0.05) . There was a strong linkage disequilibrium (LD) relationship between rs1049216 and rs6948 (D'>0.8) . Haplotype AT and GG composed of rs1049216-rs6948 increased the risk of NIHL (P<0.05) . The risk of NIHL increased with the increase of GRS (OR=2.69, P<0.05) . Conclusion: Genotype polymorphisms at rs1049216 and rs6948 (CASP3) , rs12195525 (NOX3) , rs12415607 (CASP7) may be associated with susceptibility to NIHL.
目的： 探究基因多态性对工人患噪声性听力损失（NIHL）的影响。 方法： 于2019年5月，采用病例对照研究，选取2017至2018年浙江省5所工厂噪声作业工人，选择双耳高频（3、4、6 kHz）平均听阈>25 dB（A）作为NIHL组，任一耳任一语频（0.5、1、2 kHz）听阈≤25 dB（A）作为非NIHL组，每组307人。收集噪声作业工人的一般人口学资料、职业史、纯音测听结果和口腔拭子黏膜样本，提取口腔黏膜细胞DNA。分析基因风险评分（GRS）与NIHL的关系，对单核苷酸多态性（SNP）进行基因分型，用logistic回归分析基因型与NIHL的关系，用R语言分析单体型与NIHL的关系。 结果： 校正性别、年龄、学历和工作年限后，工人携带半胱氨酸-天冬氨酸蛋白酶3基因（CASP3） rs1049216隐性模型GG基因型、rs6948隐性模型TT基因型，NADPH氧化酶3基因（NOX3） rs12195525加性模型GT基因型和显性模型TT+GT基因型工人NIHL患病风险降低（P<0.05）。携带半胱氨酸-天冬氨酸蛋白酶7基因（CASP7） rs12415607加性模型AA基因型工人NIHL患病风险增高（P<0.05）。rs1049216与rs6948间存在强连锁不平衡（LD）关系（D'>0.8），由rs1049216-rs6948组成的单体型AT和GG使NIHL患病风险增加（P<0.05）。NIHL的患病风险随GRS增加而增高（OR=2.69，P<0.05）。 结论： 工人rs1049216和rs6948（CASP3）、rs12195525（NOX3）、rs12415607（CASP7）位点基因多态性与NIHL的易感性相关。.
Keywords: Gene; Genetic risk score; Hearing loss; Noise, occupational; Polymorphism, single nucleotide.