Yang Miao, Tan Hao, Yang Qiaoling, Wang Feng, Yao Huiling, Wei Qingyi, Tanguay Robert M, Wu Tangchun
Institute of Occupational Medicine, The Ministry of Education, Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China.
Cell Stress Chaperones. 2006 Autumn;11(3):233-9. doi: 10.1379/csc-192r.1.
Severe noise exposure can induce heat shock proteins (Hsps), and exposure to moderate noise has been reported to confer protection against noise-induced damage to hearing. Whether there is any association of genetic variation in both constitutive and inducible hsp70 genes with noise-induced hearing loss (NIHL) is presently unknown. Using polymerase chain reaction-restriction fragment length polymorphism, we genotyped 3 polymorphisms (+190A/ B, +1267A/B, and +2437A/B) in the hsp70-1 (rs1043618), hsp70-2 (rs1061581), and hsp70-hom (rs2227956) genes, respectively, and investigated the associations of these polymorphisms with risk of developing NIHL in 194 automobile workers working in a similar noise environment as evaluated by audiological assessment. Multivariate logistic regression models were used to assess the associations with the risk genotypes, and Whap software was used to analyze their haplotypes. Our results showed that there was no statistically significant difference in the genotype and allele distributions of hsp70-1, hsp70-2, and hsp70-hom between the NIHL group and the normal group (P > 0.05) with and without adjustment for age, sex, smoking, history of explosive noise exposure, and cumulative noise exposure. However, haplotype analysis revealed that the Hap5 (ie, haplotype +190A/+1267B/+2437A) and Hap6 (ie, haplotype +190A/+1267B/+2437B) were significantly more frequent in the NIHL group than in the normal group (20/9, P = 0.022, and 7/0, P = 0.005, respectively). Compared with Hap1 (ie, +190A/+1267A/+2437A), Hap5 was associated with a nearly 3-fold increased risk of NIHL (adjusted odds ratio, 2.67; 95% confidence interval, 1.13-6.27). Seven of the NIHL patients had Hap6, but none of the controls had this haplotype. Our results suggest that some haplotypes of the hsp70 genes may be associated with a higher susceptibility to NIHL.
严重的噪声暴露可诱导热休克蛋白(Hsps)的产生,据报道,中度噪声暴露可对噪声引起的听力损伤起到保护作用。目前尚不清楚组成型和诱导型hsp70基因的遗传变异与噪声性听力损失(NIHL)之间是否存在关联。我们采用聚合酶链反应-限制性片段长度多态性方法,分别对hsp70-1(rs1043618)、hsp70-2(rs1061581)和hsp70-hom(rs2227956)基因中的3个多态性位点(+190A/B、+1267A/B和+2437A/B)进行基因分型,并通过听力评估,研究这些多态性与194名在相似噪声环境中工作的汽车工人发生NIHL风险的关联。采用多变量逻辑回归模型评估与风险基因型的关联,并使用Whap软件分析其单倍型。我们的结果显示,在调整年龄、性别、吸烟、爆震噪声暴露史和累积噪声暴露后,NIHL组与正常组之间hsp70-1、hsp70-2和hsp70-hom的基因型和等位基因分布无统计学显著差异(P>0.05)。然而,单倍型分析显示,NIHL组中Hap5(即单倍型+190A/+1267B/+2437A)和Hap6(即单倍型+190A/+1267B/+2437B)的频率显著高于正常组(分别为20/9,P = 0.022;7/0,P = 0.005)。与Hap1(即+190A/+1267A/+2437A)相比,Hap5与NIHL风险增加近3倍相关(调整后的优势比为2.67;95%置信区间为1.13 - 6.27)。7名NIHL患者具有Hap6,但对照组中无人具有该单倍型。我们的结果表明,hsp70基因的某些单倍型可能与NIHL的易感性较高有关。