摘要
目的探讨EYA4基因多态性与噪声性听力损失（NIHL）易感性的关系。方法在噪声暴露队列基础上，进行巢式病例一对照研究，采用1：2病例一对照设计。从2006年1月1日起，以中国河南省某钢铁企业炼钢和轧钢车间的6297名接触噪声作业工人为队列研究的源人群，随访至2015年12月31日，筛选其中双耳高频平均听阈≥40dB（A）定义为病例组，共292例，根据同性别、年龄相差不超过5岁、接触噪声工龄相差不超过2年的匹配标准，选择双耳高频平均听阈〈35dB（A）且双耳平均语频≤25aB（A）定义为对照组，确定对照584名；通过SNPscan^TM法检测EYA4基因的4个单核苷酸位点的多态性，采用多因素条件logistic回归分析模型分析EYA4基因单个位点与NIHL易感性之间的关系。并分析单体型与累积噪声暴露量（cNE）之间交互作用对NIHL易感性的作用。结果纳入调查对象的年龄为（40．1±8.4）岁，接噪工龄的M（P25，P75）为[20．3（8．4，27.3）1年，接触噪声的范围最小值～最大值为80．2～98．8dB（A），累计噪声暴露量（ONE）的最小值～最大值为86．6～111．2dB（A）·年。在调整吸烟、饮酒、高血压和身高后，在噪声暴露水平〉85dB（A）组，与GG基因型相比，携带rs3813346TT基因型发生NIHL的0R（95％CI）值为2．12（1．21～3．69）。在CNE〉98dB（A）·年组，与TGC单体型相比，携带单体型CGT发生NIHL的风险的0R（95％CI）值为0．60（0．37—0．97），而经Bonferroni检验校正后，EYA4基因型与噪声的交互作用差异没有统计学意义。结论EYA4基因多态性可能是NIHL的遗传易感性因素。
Objective To identify the association between genetic polymorphisms in the eye absent homolog 4 （EYA4） gene and noise-induced hearing loss （NIHL）. Method 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 Decl2, 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 riB（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 SNPscanTM multiplex SNP genotyping kit. Hardy-Weinberg equilibrium tests were performed using a X2 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. Results 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 OR （95% C/） value was 2.12 （1.21-3.69）. In the cumulative noise exposure〉98 dB （A） · year group, compared with haplotype TGC, haplotype CGT
出处
《中华预防医学杂志》
CAS
CSCD
北大核心
2017年第1期27-33,共7页
Chinese Journal of Preventive Medicine
基金
国家自然科学基金（81372940）
国家科技支撑计划（2014BAI12803）
