【作者】 杨杪； 谭皓； 郑建如； 王峰； 蒋长征； 何美安； 陈永文； 邬堂春；

【Author】 YANG Miao, TAN Hao,ZHENG Jianru, WANG Feng, JIANG Chang-zheng, HE Mei-an, CHEN Yong-wen, WU Tang-chun (Department of Labor Health and Enviromental Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China)

【机构】 华中科技大学同济医学院公共卫生学院劳动卫生与环境卫生学系； 东风汽车公司职业病防治所；

【摘要】 [目的]研究几种听力损失相关蛋白和热休克蛋白的基因多态性与职业性噪声暴露工人噪声性听力损失的遗传易感性之间的关系。[方法]采刚横断面流行病学研究方法,对194名职业性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;分析其CDH23、PMCA2、GSTM1、GSTT1、HSP70-1、HSP70-2、HSP70-hom、HSP60、HSF1、HSF2、和HSF2BP基因的多态性;用多元logistic回归分析对年龄、性别、吸烟、爆震史和累积噪声暴露量等因素进行校正后,计算不同基因型工人发生噪声性听力损失的危险度,并探讨基因间的交互作用;用whap软件对同一基因上的位点的多态性进行单倍型分析。[结果]校正了194名研究对象的年龄、性别、吸烟、爆震史和累积噪声暴露量等因素后,发现CDH23基因rs1227049位点的CC基因型与GG基因型相比噪声性听力损失的危险度显著升高,(调整OR=3.865,95%CI=1.076-13.886);CDH23-rs3802711位点的TT基因型与CT基因型相比噪声性听力损失的危险度有极显著性升高(调整OR=6.088,95%CI=2.485-14.917);CDH23-第七外显子的末位单核苷酸位点的GG基因型与AG基因型相比噪声性听力损失的危险度也有极显著性升高(调整OR=5.769,95%CI=2.745.12.121)。GSTT1缺失基因型噪声性听力损失的危险度显著升高(调整OR=1.952,95%CI=1.017-3.746)。还发现GSTT1基因与CDH23基因的rs1227049、rs3802711和第七外显子的末位单核苷酸位点在对噪声性听力损失的影响中存在基因与基因交互作用。对HSP70基因的单倍型分析提示由-190A(HSP70-1),-1267B(HSP70-2)和-2437A(HSP70-hom)等位基因构成的Hap5单倍型在噪声性听力损失组中明显增加,与听力正常组相比有极显著性差异(20/7,P=0.005);由-190A,-1267B和-2437B等位基因构成的Hap6单倍型只存在于噪声性听力损失组,与听力正常组相比有极显著性差异(7/0,P=0.005);Hap5和Hap6单倍型的调整OR值分别为6.392和8.449。未发现其他基因的遗传变异与研究对象噪声性听力损失的显著关联。[结论]本研究发现CDH23、GST和HSP70基因的遗传变异可显著性影响职业性噪声暴露个体噪声性听力损失的危险度,携带某些特定基因型或单体型的个体对噪声性听力损失的易感性显著升高。更多还原

【Abstract】 [Objective] To investigate the association of several hearing loss related proteins and heat shock proteins gene polymorphisms with the inherited susceptibility of noise induced hearing loss (NIHL) among the occupational noise exposed workers. [Methods] 194 workers exposed to occupational noise were drawn as the subjects in the cross-sectional epidemiology study. According to the result of audiometry, they were divided into two groups: the NIHL group and the normal group. The genotypes of CDH23、PMCA2、 GSTM1、 GSTT1、 HSP70-1、 HSP70-2、 HSP70-hom、 HSP60、 HSF1、 HSF2、 and HSF2BP genes were determined by PCR-based methods. Multiple logistic regression was used to calculate the adjusted ORs and the 95 %CI for the risk of NIHL and to analyze the gene-gene interaction. WHAP software was used to analyse the haplotypes of SNP positions on the same gene. [Results] After adjusted for age, sex, smoking, history of explosive noise exposure and cumulative noise exposure (CNE) with multiple logistic regression analysis, the risk of CDH23-rs1227049 CC genotype was found significantly increased than that of the GG genotype, the OR value of which was 3.865 , (95% confidence interval 1.076-13.886); the risk of CDH23-rs3802711 TT genotype was significantly higher than that of the CT genotype(adjusted OR = 6.088, 95% CI = 2.485-14.917); GG genotype in the terminal position of CDH23-exon 7 was also found a significantly higher risk than the AG genotype(adjusted OR =5.769, 95% CI = 2.745-12.121). The subjects with GSTT1 null genotype have significantly higher risk for NIHL than subjects with GSTT1 positive genotype (adjusted OR = 1.952, 95%CI= 1.017-3.746). The gene-gene interactions were also found among GSTT1 and CDH23 gene rs1227049, rs3802711 and the terminal position of exon 7 polymorphisms for the risk of NIHL. Haplotype analysis revealed that the Hap5 haplotype frequency, which included -190A(HSP70-1), - 1267B(HSP70-2) and -2437A(HSP70-hom) alleles, and the Hap6 haplotype frequency, which included - 190A(HSP70-1), - 1267B(HSP70-2) and -2437A(HSP70-hom) alleles, were significantly increased in NIHL group than in normal group (20/7, P =0. 005 and 7/0, P =0. 005). After adjusted for sex and cumulative noise exposure (CNE), the risk of Hap5 and Hap6 haplotypes were still found significantly increased for the risk of NIHL; the adjusted OR value was 6.392 and 8.449, respectively. [Conclusion] Significant associations between genetic polymorphisms in CDH23 , GSTT1 and HSP70 gene and the risk for NIHL were found among occupational noised-exposed workers; the individuals with certain genotypes or haplotypes might be more susceptible to noise induced hearing loss.更多还原