线粒体12 S rRNA基因、tRNA基因和细胞色素氧化酶Ⅱ基因多态性与职业人群噪声性听力损失易感性的研究

摘要

Objective To explore the relationship between mitochondrial 12 S rRNA gene variation, tRNA gene variation and cytochrome oxidase Ⅱ gene point mutations and the risk of noise-induced hearing loss (NIHL). Methods A nested case-control study was performed that followed a cohort of 7 445 noise-exposed workers in a steel factory in Henan province, China, from January 1, 2006 to December 31, 2015. Subjects whose average hearing threshold was more than 40 dB(A) in high frequency were defined as the case group, and subjects whose average hearing threshold was less than 35 dB(A) in high frequency and less than 25 dB (A) in speech frequency were defined as the control group. Subjects was recruited into the case group (n=286) and the control group (n=286) according to gender, age, job category and time of exposure to noise, and a 1∶1 case-control study was carried out. We genotyped eight single nucleotide polymorphisms in the mitochondrial 12 S rRNA gene, the mitochondrial tRNA gene and the mitochondrial cytochrome oxidase Ⅱ gene using SNPscan high-throughput genotyping technology from the recruited subjects. The relationship between polymorphic sites and NIHL, adjusted for covariates, was analyzed using conditional logistic regression analysis, as were the subgroup data. Results The average age of the recruited subjects was (40.3±8.1) years and the length of service exposure to noise was (18.6±8.9) years. The range of noise exposed levels and cumulative noise exposure (CNE) was 80.1-93.4 dB (A) and 86.8-107.9 dB (A) · year, respectively. For workers exposed to noise at a CNE level<98 dB (A) · year, smokers showed an increased risk of NIHL of 1.88 (1.16-3.05) compared with non-smokers;for workers exposed to noise at a CNE level ≥98 dB(A) · year, smokers showed an increased risk of NIHL of 2.53 (1.49-4.30) compared with non-smokers. For workers exposed to noise at a CNE level<98 dB (A) · year, the results of univariate analysis and multifactor analysis, adjusted by smoking and CNE, suggested that the risk of NIHL in workers exposed to noise carrying the GG genotype (G827A) was lower than that of NIHL workers exposed to noise carrying the AA genotype (G827A) [OR (95% CI) were 0.18 (0.04-0.82) and 0.19 (0.04-0.88), respectively]. Conclusion Smoking increased the risk of NIHL in the present study. For workers subjected to a CNE<98 dB(A)·year, the mitochondrial genetic variant G827A was found to be significantly associated with the risk of NIHL.%目的：探讨线粒体12 S rRNA基因、tRNA基因和细胞色素氧化酶Ⅱ基因多态性与职业性噪声听力损失(NIHL)发生风险的关系。方法从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7445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≥40 dB（A）定义为病例组，选择双耳高频平均听阈<35 dB（A）且双耳平均语频≤25 dB（A）定义为对照组，并严格按年龄、接噪工龄、性别、工种因素，进行1∶1病例-对照配对，最终选取病例组286例和对照组286名。采用SNPscanTM法对研究对象的线粒体12 S rRNA基因、tRNA基因和细胞色素氧化酶Ⅱ基因的8个位点进行基因分型。采用多因素条件logistic回归模型分析不同单核苷酸多态性与NIHL发病的关系，并在对累积噪声暴露量（CNE）进行分层后，分析不同噪声暴露水平、人群特征对NIHL发病的影响，最后分析了调整吸烟和CNE后，不同单核苷酸多态性与NIHL发生风险之间的关系。结果调查对象的年龄为（40.3±8.1）岁，接噪工龄为（18.6±8.9）年，接触噪声的范围最小值~最大值为80.1~93.4 dB（A），CNE的最小值~最大值为86.8~107.9 dB（A）·年。在CNE<98 dB（A）·年人群中，与不吸烟人群相比，吸烟人群发生NIHL的OR（95%CI）为1.88(1.16~3.05)；在CNE≥98 d(B)A·年人群中为OR（95%CI）为2.53(1.49~4.30)。CNE<98 dB（A）·年的噪声作业工人，与G827A位点不携带GG基因型者相比，携带G827A位点GG基因型者发生NIHL的OR（95%CI）为0.18(0.04~0.82)。在调整了吸烟、CNE之后，与G827A位点不携带GG基因型者相比，携带G827A位点GG基因型者发生NIHL的OR（95%CI）为0.19(0.04~0.88)。结论吸烟可增加职业噪声作业工人的NIHL的发生风险，对于CNE<98 dB（A）·年研究对象，线粒体的G827A位点变异可能与NIHL的发生风险有关。