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[CDH23基因与噪声性听力损失风险的关系研究]

[Relationship research among CDH23 gene and the risk of noise-induced hearing loss].

作者信息

Jiao J, Gu G Z, Chen G S, Zhang H L, Wu H, Li Y H, Zhou W H, Yu S F

机构信息

Henan Provincial Institute for Occupational Health, Zhengzhou 450052, China.

Wugang Institute for Occupational Health, Wugang 462500, China.

出版信息

Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi. 2020 Feb 20;38(2):84-90. doi: 10.3760/cma.j.issn.1001-9391.2020.02.002.

Abstract

To explore the relationship among CDH23 gene variation and the risk of noise-induced hearing loss (NIHL) . The nested case-control study was performed and this study followed a cohort of 6297 noise-exposed workers in a steel factory of Henan province in China from January 1, 2006 to December 31, 2015. In July 2019, subjects whose average hearing threshold were more than 40 dB in high frequency were defined as the case group, and subjects whose average hearing threshold were less than 35 dB in high frequency and less than 25 dB in speech frequency were defined as the control group. A nested case-control study which included 572 subjects was carried out, in which subjects consisted of 286 cases and 286 controls. 18 single nucleotide polymorphisms (SNPs) in CDH23 were selected and genotyped, then we analyzed the association among SNPs in CDH23, haplotypes in CDH23 and NIHL risk. Logistic regression was performed to analyze the main effects of SNPs and the interactions between CNE and SNPs adjusting cumulative noise exposure (CNE) , smoking, drinking, physical exercise and hypertension. Moreover, the association between haplotypes in CDH23 and NIHL risk were also analyzed. We ananlyzed the relationship amongst different SNP groups and NIHL risk using the generalized multifactor dimensionality reduction (GMDR) method. The results suggested that significant associations were observed for rs3802711, rs3752751, rs3752752, rs11592462, rs10762480, rs3747867 for NIHL overall and/or various CNE strata by adjusting CNE, smoking, drinking, physical exercise and blood pressure. For rs3802711, workers exposure to noise carrying the AA/GA genotype of rs3802711 increased risk of NIHL than those carrying GG genotype (=3.121; 95%:1.054-9.239, =0.035) in overall; In the stratified analysis of CNE (>97 dB (A) ·year at rs3802711 locus, workers exposure to noise carrying GA genotype (=2.056; 95%:1.2263.448, =0.006) and GA+AA/GA genotype (=2.221; 95%:1.3403.681, =0.002) increased NIHL risk. For rs11592462, workers exposure to noise carrying the GG genotype of rs11592462 increased risk of NIHL than those carrying CC genotype in overall (=3.951; 95%:1.104-14.137, =0.04) ; workers exposure to noise carrying the GG genotype of rs11592462 increased risk of NIHL than those carrying CG+CC genotype in overall (=4.06; 95%:1.145-14.391, =0.03) . After adjusting CNE, smoking, drinking, physical exercise and blood pressure, the haplotypes of CDH23 rs1227049, rs10999947, rs3752752, rs3752751, rs10762480, rs3802711, rs11592462, rs10466026, rs4747194, rs4747195 were not associated with the risk of NIHL. GMDR analysis showed no association between SNP combination and NIHL risk after adjusting CNE, smoking, drinking, physical exercise and blood pressure. Gene polymorphisms in CDH23 might associate significantly with the risk of NIHL.

摘要

为探讨CDH23基因变异与噪声性听力损失(NIHL)风险之间的关系。进行了巢式病例对照研究,该研究对2006年1月1日至2015年12月31日期间河南省一家钢铁厂的6297名噪声暴露工人进行了队列随访。2019年7月,将高频平均听阈大于40 dB的受试者定义为病例组,将高频平均听阈小于35 dB且言语频率平均听阈小于25 dB的受试者定义为对照组。开展了一项包含572名受试者的巢式病例对照研究,其中受试者包括286例病例和286名对照。选择了CDH23基因中的18个单核苷酸多态性(SNP)进行基因分型,然后分析了CDH23基因中的SNP、单倍型与NIHL风险之间的关联。进行逻辑回归分析以调整累积噪声暴露(CNE)、吸烟、饮酒、体育锻炼和高血压后分析SNP的主要效应以及CNE与SNP之间的相互作用。此外,还分析了CDH23基因单倍型与NIHL风险之间的关联。我们使用广义多因素降维(GMDR)方法分析了不同SNP组与NIHL风险之间的关系。结果表明,通过调整CNE、吸烟、饮酒、体育锻炼和血压,在NIHL总体和/或不同CNE分层中,rs3802711、rs3752751、rs3752752、rs11592462、rs10762480、rs3747867存在显著关联。对于rs3802711,携带rs3802711的AA/GA基因型的噪声暴露工人患NIHL的风险高于携带GG基因型的工人(总体上:比值比=3.121;95%置信区间:1.054 - 9.239,P = 0.035);在rs3802711位点CNE(>97 dB(A)·年)的分层分析中,携带GA基因型的噪声暴露工人(比值比=2.056;95%置信区间:1.2263.448,P = 0.006)和携带GA + AA/GA基因型的工人(比值比=2.221;95%置信区间:1.3403.681,P = 0.002)患NIHL的风险增加。对于rs11592462,携带rs11592462的GG基因型的噪声暴露工人患NIHL的风险高于携带CC基因型的工人(总体上:比值比=3.951;95%置信区间:1.104 - 14.137,P = 0.04);携带rs11592462的GG基因型的噪声暴露工人患NIHL的风险高于携带CG + CC基因型的工人(总体上:比值比=4.06;95%置信区间:1.145 - 14.391,P = 0.03)。调整CNE、吸烟、饮酒、体育锻炼和血压后,CDH23基因的rs1227049、rs10999947、rs3752752、rs3752751、rs10762480、rs3802711、rs11592462、rs10466026、rs4747194、rs4747195单倍型与NIHL风险无关。GMDR分析表明,调整CNE、吸烟、饮酒、体育锻炼和血压后,SNP组合与NIHL风险无关联。CDH23基因多态性可能与NIHL风险显著相关。

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