噪声性听力损失易感性与SOD1单倍型的关联研究

Association between Haplotypes in SOD 1 and Noise-induced Hearing Loss

目的探讨噪声性听力损失(noise-induced hearing loss,NIHL)易感性与中国汉族人群铜锌超氧化物歧化酶(SOD1)基因存在的单倍型之间的关联。方法利用病例对照研究,通过比较在同一噪声暴露强度下噪声作业人员的左耳3 000 Hz频段听阈位移情况,筛选出听阈位移最大的10%个体作为易感人群组,共201例;听阈位移最小的10%个体作为耐受人群组,共202例。并进行相关的职业卫生调查和问卷调查。抽取易感人群和耐受人群空腹外周静脉血5 ml用于Qiagcn试剂盒方法抽提基因组DNA,TaqMan探针法化学荧光等位基因鉴别试验检测单核苷酸多态性(SNP),用Haploview软件进行单倍型的计算和2组比较。结果 NIHL易感人群噪声暴露强度中位数和上下四分位数间距为86.90(83.05,92.90),耐受人群噪声暴露强度中位数和上下四分位数间距为86.90(83.73,92.70),2组比较,差异无统计学意义,P>0.05。易感人群3 000 Hz左耳平均听阈位移水平为(40.23±9.53)dB,显著高于耐受人群的听阈位移水平(16.15±2.58)dB,P<0.01;所有SNPs位点基因型频率在2组人群中分布均符合遗传学Hardy-Weinberg平衡,与分布频率最高的单倍型CGGA相比,单倍型TATG是NIHL的保护因素,OR值和95%CI分别为0.56(0.38,0.82);单倍型CATG是NIHL的危险因素,OR值和95%CI为1.58(1.08,2.31)。结论在中国汉族人群中,NIHL易感性与SOD1单倍型有关。

[Objective]To observe the association between Haplotypes in SOD1 and noise-induced hearing loss（NIHL） in Chinese han population. [Methods]A case control study was design to compare the threshold shift of left ear at 3 000 Hz among workers exposed to the same noise intensity.The 10% sensitive workers with maximum threshold shift（201cases） and 10% resistant workers with minimum threshold shift（202 cases） were selected.A questionnaire was designed to carry out an investigation,and an occupational health survey was used to identify the occupational risk factors.Genomic DNA was extracted from peripheral blood cells samples by using standard procedures of Qiagen kit.SNPs were detected by using standard procedures of TaqMan probe allele identification method.Haplotypes were analyzed by the Haploview software. [Results]There were no significant difference in noise exposure levels between the NIHL sensitive workers and resistant ones [86.90（83.05,92.90） dB vs.86.90（83.73,92.70） dB]（P0.05）,but the threshold shift at 3 000Hz in left ear were significantly higher in NIHL sensitive workers than in the resistant workers（40.23±9.53 dB vs.16.15±2.58 dB）（P0.01）.The genotype frequency of every SNPs locus in each group was in line with Hardy-Weinberg equilibrium.Compared with haplotype CGGA with highest distribution frequency,hyplotype TATG was a protective factor to NIHL,whereas CATG was a risk factor.The OR and 95%CI of TATG and CATG were 0.56（0.38,0.82）,1.58（1.08,2.31） respectively. [Conclusion]In Chinese Han population,the haplotypes in SOD1 may be associated with the susceptibility to NIHL.