Yang Q Y, Xu X R, Jiao J, Zheng Y X, He L H, Yu S F, Gu G Z, Chen G S, Zhou W H, Wu H, Li Y H, Zhang H L, Zhang Z R
Department of Occupational and Environment, Peking University School of Public Health, Beijing 100191, China.
Zhonghua Yu Fang Yi Xue Za Zhi. 2017 Jan 6;51(1):27-33. doi: 10.3760/cma.j.issn.0253-9624.2017.01.007.
To identify the association between genetic polymorphisms in the eye absent homolog 4 (EYA4) gene and noise-induced hearing loss (NIHL). A nested case control study was conducted based on a cohort of noise-exposed subjects. In total, 292 cases were selected from a steel factory from 6 297 subjects during Jan 1, 2006 to Dec 12, 2015,who had an average hearing threshold of more than 40 dB(A); 584 matched control subjects for each case were designated on the basis of matched criteria including same gender, age (±5 years) and duration of exposure to noise (±2 years). What's more, the control group had an average hearing threshold of less than 35 dB(A) in high frequency and less than 25 dB(A) in speech frequency. Four single nucleotide polymorphisms (SNPs) of the EYA4 gene were genotyped using a SNPscan multiplex SNP genotyping kit. Hardy-Weinberg equilibrium tests were performed using a χ test for goodness-of-fit for each SNP among the control group, and the effects of genotypes of the EYA4 gene on NIHL were analyzed by logistic regression. The haplotypes were established and their frequencies in the two groups were assessed using Haploview 4.2 and Phase 2.1 software, and interactive effects between haplotypes and cumulative noise exposure were analyzed. The average age of the subjects was (40.1±8.4) years and the average number of noise-exposed working years was 20.3 (8.4, 27.3) years. The range of noise exposure levels and the cumulative noise exposure were 80.2- 98.8 dB (A) and 86.6- 111.2 dB(A) · year, respectively. After adjustment for covariates including height, blood pressure, drinking status and smoking status, in the noise intensity>85 dB (A) group, subjects carrying the rs3813346 TT genotype had a higher NIHL risk than those carrying the GG genotype, and the adjusted (95% ) value was 2.12 (1.21- 3.69). In the cumulative noise exposure>98 dB (A) · year group, compared with haplotype TGC, haplotype CGT showed a protective effect in the development of NIHL, with an adjusted (95% ) value of 0.60 (0.37-0.97), however, the significance of intercation between EY4 gene of noise was lost after Bonferroni correction. Genetic polymorphism in the EYA4 gene may be a genetic susceptibility factor for NIHL.
确定眼缺失同源物4（EYA4）基因的基因多态性与噪声性听力损失（NIHL）之间的关联。基于一组噪声暴露受试者进行了一项巢式病例对照研究。2006年1月1日至2015年12月12日期间，从一家钢铁厂的6297名受试者中总共选取了292例病例，这些病例的平均听力阈值超过40 dB（A）；根据匹配标准（包括相同性别、年龄（±5岁）和噪声暴露持续时间（±2年））为每个病例指定584名匹配的对照受试者。此外，对照组的高频平均听力阈值低于35 dB（A），语音频率平均听力阈值低于25 dB（A）。使用SNPscan多重SNP基因分型试剂盒对EYA4基因的四个单核苷酸多态性（SNP）进行基因分型。使用χ²拟合优度检验对对照组中的每个SNP进行Hardy-Weinberg平衡检验，并通过逻辑回归分析EYA4基因的基因型对NIHL的影响。构建单倍型，并使用Haploview 4.2和Phase 2.1软件评估两组中的单倍型频率，并分析单倍型与累积噪声暴露之间的交互作用。受试者的平均年龄为（40.1±8.4）岁，平均噪声暴露工作年限为20.3（8.4，27.3）年。噪声暴露水平范围和累积噪声暴露分别为80.2 - 98.8 dB（A）和86.6 - 111.2 dB（A）·年。在对包括身高、血压、饮酒状况和吸烟状况等协变量进行调整后，在噪声强度>85 dB（A）组中，携带rs3813346 TT基因型的受试者比携带GG基因型的受试者患NIHL的风险更高，调整后的（95%）值为2.12（1.21 - 3.69）。在累积噪声暴露>98 dB（A）·年组中，与单倍型TGC相比，单倍型CGT在NIHL的发生中显示出保护作用，调整后的（95%）值为0.60（0.37 - 0.97），然而，经Bonferroni校正后，EY4基因与噪声之间的交互作用的显著性丧失。EYA4基因的基因多态性可能是NIHL的遗传易感因素。
