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[原钙黏蛋白15基因变异与职业性噪声性听力损失之间的关联]

[Association between variations in protocadherin 15 gene and occupational noise-induced hearing loss].

作者信息

Xu X R, Yang Q Y, Jiao J, Zheng Y X, He L H, Yu S F, Gu G Z, Chen G S, Zhou W H, Wu H, Li Y H, Zhang H L, Zhang Z R

机构信息

Department of Occupational and Environmental Health, School of Public Health, Peking University, Beijing 100191, China.

出版信息

Zhonghua Yu Fang Yi Xue Za Zhi. 2017 Jan 6;51(1):20-26. doi: 10.3760/cma.j.issn.0253-9624.2017.01.006.

Abstract

The aim of this study was to investigate whether genetic variability in the protocadherin 15 (PCDH15) gene may correspond with increased susceptibility to noise-induced hearing loss (NIHL) in a Chinese population. A nested case-control study was performed that followed a cohort of 7 445 noise-exposed workers in a steel factory of Henan province in China from January 1, 2006 to December 31, 2015. In this study, 394 cases who had an average hearing threshold of more than 40 dB (A) in high frequency were defined as the case group, and 721 controls who had an average hearing threshold of less than 35 dB (A) in high frequency and less than 25 dB (A) in speech frequency were defined as the control group. A questionnaire was completed by participants and a physical test was also conducted. SNP genotyping was performed using the SNPscan Kit. Multivariate unconditional logistic regression additive models were used to analyze the genotypes in different groups, and the association with NIHL. Unconditional logistic regression models were used to assess the associations between the genotypes and NIHL. The average age of study participants was (40.5±8.3) years and the median number of noise-exposed working years (, ) was 21.1 (9.1, 27.3). The range of noise exposed levels and the levels of cumulative noise exposure (CNE) were 80.1- 98.8 dB(A) and 86.6- 111.2 dB(A), respectively. Only the distribution of the genotypes (TT/CC/CT) of rs11004085 in the PCDH15 gene showed a significant difference between the case and control groups (0.049). In the case group, the distribution was 370 (93.9%), 24 (6.1%) and 0; in the control group, the distribution was 694 (96.3%), 23 (3.2%) and 1 (0.1% ). After smoking, drinking, hypertension, height and CNE adjustment, compared with the TT genotype individuals with the CC/CT genotype had a 1.90-fold increased risk of NIHL (95% 1.06- 3.40). After stratified these data by the noise exposure level or CNE when the noise exposure level was>85 dB (A), compared with cases with the AA genotype of rs10825113, individuals with the GA/GG genotype had a 2.63-fold increased risk of NIHL (95% 1.12- 6.14). When the CNE was ≤ 98 dB(A), compared with cases with the TT genotype of rs11004085, individuals with the CC/CT genotype had a 2.96-fold increased risk of NIHL (95% 1.33- 6.56). However, these differences were not significant after Bonferroni correction had been applied. The results confirmed that genetic variation within the PCDH15 gene may affect the susceptibility to NIHL.

摘要

本研究旨在调查原钙黏蛋白15(PCDH15)基因的遗传变异性是否与中国人群中噪声性听力损失(NIHL)易感性增加相关。在中国河南省一家钢铁厂,对2006年1月1日至2015年12月31日期间的7445名噪声暴露工人队列进行了一项巢式病例对照研究。本研究中,高频平均听阈超过40 dB(A)的394例被定义为病例组,高频平均听阈低于35 dB(A)且言语频率平均听阈低于25 dB(A)的721例被定义为对照组。参与者完成了一份问卷并进行了体格检查。使用SNPscan试剂盒进行单核苷酸多态性(SNP)基因分型。采用多变量非条件逻辑回归加法模型分析不同组的基因型及其与噪声性听力损失的关联。非条件逻辑回归模型用于评估基因型与噪声性听力损失之间的关联。研究参与者的平均年龄为(40.5±8.3)岁,噪声暴露工作年限中位数为21.1(9.1,27.3)年。噪声暴露水平范围和累积噪声暴露(CNE)水平分别为80.1 - 98.8 dB(A)和86.6 - 111.2 dB(A)。仅PCDH15基因中rs11004085的基因型(TT/CC/CT)分布在病例组和对照组之间存在显著差异(0.049)。病例组中,分布为370(93.9%)、24(6.1%)和0;对照组中,分布为694(96.3%)、23(3.2%)和1(0.1%)。在对吸烟、饮酒、高血压、身高和累积噪声暴露进行校正后,与TT基因型个体相比,携带CC/CT基因型的个体患噪声性听力损失的风险增加了1.90倍(95%置信区间为1.06 - 3.40)。当按噪声暴露水平或累积噪声暴露对这些数据进行分层时,当噪声暴露水平>85 dB(A)时,与rs10825113的AA基因型病例相比,携带GA/GG基因型的个体患噪声性听力损失的风险增加了2.63倍(95%置信区间为1.12 - 6.14)。当累积噪声暴露≤98 dB(A)时,与rs11004085的TT基因型病例相比,携带CC/CT基因型的个体患噪声性听力损失的风险增加了2.96倍(95%置信区间为1.33 - 6.56)。然而,在应用Bonferroni校正后,这些差异并不显著。结果证实,PCDH15基因内的遗传变异可能影响噪声性听力损失的易感性。

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