噪声性听力损失易感基因的研究进展

噪声性听力损失是现阶段全球最主要的职业性损伤之一.以往的研究显示,噪声的易感性存在个体差异,本文综述报道目前国内外关于基因多态性与噪声性听力损失之间关系的现有研究状况.     

噪声性听力损失易感基因多态性的研究进展

近年来,大量研究致力于鉴定可能与噪声性听力损失(noise-induced hearing loss,NIHL)易感性相关的候选基因单核苷酸多态性(single nucleotide polymorphisms,SNPs)的探讨,但尚未见对该领域研究成果的归纳总结.通过全面系统的检索,本文汇总了与NIHL相关的SNPs...     

噪声性听力损失易感基因研究现况

噪声性听力损失是危害劳动者健康的重要职业性疾患.研究表明个体对噪声的易感性不同,人们对与其有关的基因改变进行了大量研究,本文总结了噪声性听力损失易感基因的现有研究情况,并对其研究方法也进行了综述.     

热休克蛋白60基因多态性与噪声性听力损失易感性的关系

目的探讨热休克蛋白60（HSP60）基因多态性与噪声性听力损失的关系。方法采用横断面流行病学研究方法,对194名噪声暴露作业工人进行调查和听力测试,按听力学评价的结果将其分为听力损失组和听力正常组;用等位基因特异扩增法（ASA）和多聚酶链反应一限制性片断长度多态性法（PCR-RFLP）检测其HSP60基因上rs11551350和rs2340690两个单核苷酸位点的多态性。结果rs11551350位点在93名噪声性听力损失的工人中CG、AA和AG基因型的频率分别为1．1％、9．7％和89．2％,等位基因G和A的频率为45．7％和54．3％;在101名听力正常的工人中,基因型频率分别为5．9％（CG）、5．9％（AA）和88．1％（AG）,等位基因频率为50．0％（G）和50．0％（A）。rs2340690位点在噪声性听力损失组CC、TT和CT基因型的频率分别为51．6％、7．5％和40．9％,等位基因C和T的频率为72．0％和28．0％;在听力正常组的基因型频率分别为45．5％CC）、4．0％（TT）和50．5％（CT）;等位基因频率为70．8％（C）和29．2％（T）。两位点的基因型分布及其等位基因频率在噪声性听力损失组与听力正常组之间差异均无显著性（P〉0．05）。采用多元Logistic回归对两组问年龄、性别、吸烟状况、爆震史和累积噪声暴露量等因素进行校正后,未发现两位点中任一基因型的噪声性听力损失的危险度有显著性升高（P〉0．05）。结论HSW60基因的rs11551350和rs2340690两个单核苷酸位点的多态性可能不是噪声性听力损失的遗传易感性因素。     

噪声性听力损失易感人群筛选方法探讨

目的 探讨噪声性听力损失的易感、耐受人群筛选方法,为今后研究提供帮助.方法 选择噪声暴露强度在75～120 dB范围内的企业噪声作业工人为研究对象.进行现场职业卫生学调查、收集工人基本情况和工人听阈水平检测的资料,采用国内外筛选噪声性易感和耐受人群的3种方法,判断不同方法在筛选易感人群和耐受人群的情况.通过配对x2检验做两两比较,并且对样本的噪声暴露情况、一般情况的均衡性以及噪声性听阈位移情况为依据,判断哪种方法更好.结果 各个方法筛选出来的易感人群和耐受人群的噪声暴露情况,基本情况,左右耳听阈水平都有较好的均衡性,配对x2检验发现两两之间差异无统计学意义(P＞0.05).但从专业的角度比较,各数值间存在较多错配情况,高频听阈情况有统计学差异,方法B和方法C结果较为相近且优于方法A.结论 现今我国工人年轻化,自我保护意识加强,个体防护措施做的较之前有很大的提高,采用方法B更适合作为我国现阶段噪声性听力损失人群的特征.     

过氧化氢酶基因单核苷酸多态性与职业人群噪声性听力损失易感性

目的探讨过氧化氢酶(catalase, CAT)基因单核苷酸多态性与职业噪声接触人群噪声性听力损失(noise-induced hearing loss, NIHL)易感性间的关系。方法基于2006—2015年对河南省某钢铁厂职业噪声接触工人的队列研究,采用1∶1匹配的巢式病例-对照研究方法,从队列中选出双耳高频平均听阈≥40 dB(HL),共286人,根据工种、性别相同,年龄相差不超过5岁且接触噪声工龄相差不超过2年进行匹配,在该队列中选出听力正常的对照组286人。用中高通量单核苷酸多态性分型检测技术(SNPscan^TM法)检测CAT基因的8个单核苷酸位点的多态性,采用多因素条件Logistic回归法分析CAT基因8个单核苷酸多态性位点与NIHL易感性之间的关系。结果 CAT基因rs208679位点的显性模型[(GA+GG)/AA]下,携带GA或GG基因型的个体患NIHL的风险是携带AA基因型个体的1.431倍(95%CI 1.020～2.009),经检验P=0.038。结论 CAT基因rs208679位点突变型等位基因G可能为NIHL易感性的危险因素之一。     

CDH23基因位点多态性与噪声性听力损失相关性的Meta分析

目的 运用Meta分析的方法评价CDH23基因rs1227049、rs1227051、rs3802711和Exon7多态性与噪声性听力损失(noise-induced hearing lose,NIHL)的相关性.方法 检索PubMed、Embase、Web of Science、中国知网、维普、万方数据库,收集有关C...     

STAT3 rs1053005位点与miR-452-3p靶向结合及其基因多态性与噪声性听力损失的关联性

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...     

噪声性听力损失与耳蜗外毛细胞Prestin蛋白的相关性分析

目的探讨噪声性听力损失(NIHL)与耳蜗外毛细胞Prestin蛋白表达的关系。方法将60只成年豚鼠随机分5组,除对照组外分别予以不同噪声声压级(85、95、105、115 d B SPL)的高斯白噪声暴露(28 d,6 h/d),而后检测听性脑干反应(ABR)以确定听阈位移水平,同时进行耳蜗病理学检查,采用免疫组化法分析耳蜗外毛细胞Prestin蛋白表达水平。结果各组豚鼠平均永久性听阈位移水平变化随着噪声暴露声压级的增强而增加(F=308.655,P0.01),强噪声声压级组(105 d B SPL)豚鼠的病理形态学显示明显的毛细胞损失,Prestin蛋白表达水平在高于95 d B SPL时随着噪声暴露声压级的增加而上调(F=700.072,P0.01)。结论耳蜗外毛细胞Prestin的表达增高,与耳蜗外毛细胞损失程度有关。     

CASP3和CASP7基因多态性与噪声性听力损失易感性关系

目的 探讨细胞凋亡通路相关基因CASP3和CASP7多态性与中国汉族人群噪声性听力损失（NIHL）易感性之间的关联。方法 研究对象来自2014年杭州市1 549名噪声接触工人听力损失的横断面调查,采用1：1配对病例对照研究,病例组为电测听双耳高频平均听阈>25 dB（A）的工人,对照组为性别、年龄、接噪工龄、工作岗位与病例匹配且双耳所有频段听阈均≤25 dB（A）的工人,共272对。PCR-LDR法检测2个SNP位点的基因型。采用多因素条件logistic回归模型分析SNP位点与NIHL的关联,并以叉生分析计算基因-环境交互作用。结果 χ²检验分析发现,CASP3基因rs1049216等位基因（C、T）频率组间分布有统计学差异（OR=0.68,95%CI=0.50~0.93）,而基因型频率组间差异无统计学意义（P>0.05）;CASP7基因rs10787498等位基因及基因型频率组间分布均无统计学意义（P>0.05）;多因素条件logistic回归显示,CASP3基因rs1049216中,与野生基因型CC相比,突变基因型（CT+TT）为NIHL的保护因素（调整OR=0.65,95%CI=0.43~0.97）;叉生分析表明rs1049216位点与文化程度、睡眠时间存在交互作用（P≤0.001）,NIHL的危险性降低（OR值变小）。结论 CASP3基因rs1049216位点可能与中国汉族人群NIHL易感性有关,且可能与文化程度、睡眠时间存在交互作用。     

钙黏素23基因多态性与噪声性听力损失易感性关系研究

目的探讨钙黏素23(CDH23)基因多态性与噪声性听力损失易感性关系。方法采用病例对照研究方法对254名接触噪声工人进行研究,聚合酶链反应-限制性片断长度多态性方法检测CDH23基因单核苷酸多态性位点rs1227049和rs1227051的多态性。结果rs1227049位点在听损组CC、CG和GG基因型频率分别为39.4%、15.0%和45.6%,等位基因C和G的频率分别为46.9%和53.1%;对照组3种基因型的频率分别为51.2%、19.7%和29.1%,等位基因C和G的频率分别为60.9%和39.1%。rs1227051位点在听损组TT、CT和CC基因型频率分别为82.7%、17.3%和0,等位基因T和C的频率分别为91.3%和8.7%。对照组3种基因型的频率分别为89.0%、11.0%和0,等位基因T和C的频率分别为87.0%和13.0%。两位点的基因型分布及其等位基因频率在听损组和对照组之间差异均无统计学意义(P>0.05)。采用多因素Logistic回归分析对个体间年龄、工龄和累积噪声暴露量等因素进行校正后,也未发现两个单核苷酸位点任一基因型的改变会引起噪声性听力损失的危险度有显著性提高(P>0.05)。结论本研究还不能认为CDH23基因rs1227049和rs1227051两个单核苷酸多态性位点是噪声性听力损失易感性的危险因素。     

Association between noise-induced hearing loss and tinnitus

The objective of this study was to verify an association between noise-induced hearing loss (NIHL) and tinnitus in workers exposed to occupational noise. Workers with a history of work noise exposure who attended two audiology outpatient clinics were interviewed and evaluated. The statistical association between NIHL and tinnitus was evaluated using an adjusted linear regression model, with tinnitus as the dependent variable and NIHL, classified into six levels, as the independent variable, with age and length of noise exposure as covariates. Data were collected from 284 workers between April and October, 2003, in Bauru, S?o Paulo State, Brazil. Tinnitus was observed to increase with the progression of auditory damage, controlled by age and length of noise exposure. These results suggest that investment in hearing conservation programs is needed, especially for source noise emission control and for intervention in hearing loss progression that is caused by noise exposure, in order to maintain auditory health and reduce the associated symptoms.     

GSTM1和GSTT1基因多态性与噪声性听力损失易感性的关系

目的探讨GSTM1和GSTT1基因多态性与噪声性听力损失易感性的关系。方法采用病例对照研究方法和多重聚合酶链反应(PCR)技术检测听损组123(118)例和对照组123(114)例的GSTM1和GSTT1基因缺失型频率,以2检验检测听损组和对照组基因型频率的差异。结果GSTM1基因在听损组和正常组的缺失率分别为69.1%和56.1%,差异具有统计学意义(P<0.05)。GSTM1(-)基因型携带者发生噪声性听力损失的危险性是携带GSTM1( )基因型者的1.75倍。GSTT1基因在听损组和正常组的缺失率为50.8%和57.9%,差异没有统计学意义(P>0.05)。联合分析表明,携带GSTM1(-)和GSTT1(-)基因型者发生噪声性听力损失的危险性虽稍高于携带GSTM1( )和GSTT1( )基因型者(OR=1.11,2=0.16,P>0.05),但差异无统计学意义,由此认为GSTM1和GSTT1基因之间可能不存在联合作用。结论GSTM1基因缺失可能是发生噪声性听力损失的易感因素之一。     

Occupational noise-induced hearing loss

Occupational noise-induced hearing loss is, at least in theory,preventable. One way to assess the problem and whether preventativemeasures are effective is to assess employees' hearing. In orderto minimize cost and time off work this can be carried out effectivelyin the workplace as long as certain conditions are met.     

两种评价噪声性听觉损伤易感性方法的比较

目的比较两种评价噪声性听觉损伤易感性的方法。方法通过对103只豚鼠110dB(A)3h噪声暴露后的暂时性听阈偏移(TTS)进行统计学分析,作左右耳TTS均值频数分布图,探讨其分布规律;分别用百分位数法和正态分布法计算噪声暴露后豚鼠左右耳TTS均值90%参考值范围,在此基础上判定噪声性听觉损伤易感与不易感豚鼠,并对两种方法进行比较分析。结果左右耳TTS均值90%参考值范围,百分位数法计算结果为18.2～31.4dB,易感和不易感豚鼠分别为7只和6只;正态分布法计算结果为14.6～31.8dB,易感和不易感豚鼠分别为7只和1只。结论百分位数法更适合用于豚鼠噪声性听觉损伤易感性的评价。     

线粒体DNA缺失与噪声性听力损失关系的分析

目的探讨mtDNA4977缺失与噪声性听力损失关系。方法采用病例对照研究方法对157名接噪工人进行调查,调查其噪声暴露及听力情况,并将其分两组,听损组79人、正常组78人,用巢式PCR技术分别检测两组的mtDNA4977缺失情况,以χ2检验进行组间基因缺失频率的比较。结果听损组和正常组间年龄、噪声暴露强度和累积噪声暴露量比较差异均有统计学意义(均P<0.05),两组mtDNA4977缺失率均为94.9%,差异无统计学意义(P>0.05)。结论未发现携带mtDNA4977缺失基因型的个体能提高对噪声性听力损失的易感性。     

Evaluation of individual susceptibility to noise-induced hearing loss in textile workers in China

The authors applied noise exposure and audiometry information collected on 156 Chinese textile workers to develop a method of identifying individuals susceptible to noise-induced hearing loss. They estimated noise-induced hearing threshold shift (NIHTS) by averaging the adjusted hearing thresholds at 3, 4, and 6 kHz of both ears, and they fitted a quadratic model to describe the dose-response relationship between cumulative noise exposure and NIHTS. The residual between the actual NIHTS and the model-predicted NIHTS indicated susceptibility. A comparison of the 20% of the subjects with the greatest residuals (those who were susceptible to hearing loss) with the 20% of the subjects with the smallest residuals (those who were resistant to hearing loss) revealed that the former had poorer hearing, although the noise exposures were similar. The identified susceptible individuals also had the poorest hearing thresholds within each subgroup of homogenous noise exposures. With their model-based procedure, the authors were able to identify individuals susceptible to noise-induced hearing loss from subjects with heterogeneous noise exposures.     

Toxic encephalopathy and noise-induced hearing loss

In several laboratory animal studies, it has been documented that the hearing, vision, and brain can be injured due to exposure to organic solvents. This finding formed the background for a pilot study (n=16) aimed at identifying new ways of qualifying diagnostics, treatment, and rehabilitation of patients suffering from brain injury due to exposure to organic solvents, also referred to as toxic encephalopathy. Diagnosing toxic encephalopathy is complicated because the symptoms of this type of diffuse brain injury are non-specific. So, it was initially hypothesised that some of the difficulties involved in diagnosing toxic encephalopathy could be minimized by extending the diagnostic procedure. Apart from clinical interviewing and neuropsychological testing, the diagnosis should include the examination of hearing and vision. This will help in achieving new measures that could improve in diagnosing toxic encephalopathy with more certainty. On the basis of ranking, only one patient in the pilot study was considered to have a normal neuropsychological test profile, which was defined as a test profile without any marked deviations when compared with a normal population. A total of 10 patients were considered to have "discrete problems." These patients had a test profile showing either a few strikingly negative results or an array of results slightly below the expected level when compared with a normal population. A total of four patients were considered to suffer from "moderate problems" and one patient from "severe problems." The patients with "moderate problems" and "severe problems" showed consistent negative results and an unambiguous negative test profile. However, the overall results of all neuropsychological examinations performed revealed a dispersed picture. Quite remarkably, all the 13 patients who had their hearing examined showed a loss of hearing, 7 patients complained about tinnitus, and all patients had a history of exposure to both noise and organic solvents, which had not been observed at the initial examination, but seemed to have serious implications for their prognosis and future life.