The Relationship Between Occupational Noise-induced Hearing Loss And Single Nucleotide Polymorphisms Of Gene HSP70

Back groundNoise-induced hearing loss(NIHL) is the second most frequent form of sensorineural hearing loss after age-related hearing loss. When exposed to the same noise, some workers developed noise-induced hearing loss while the others did not, suggesting that NIHL may be associated with genetic factors. Heat shock proteins are a kind of functional proteins, whose expression would rise when cells under the stimulations such as physiological stress, ototoxic drugs, high temperature and noise. As molecular chaperones, the 70-k Da heat shock proteins(HSP70) are well known to have functions related to stress tolerance. It was reported that the susceptibility of noise-hearing loss may be associated with single nucleotide polymorphisms of HSP70 gene. This study is to explore the relationship between the single nucleotide polymorphisms in loci of rs1043618, rs2075800 and rs2763979 of HSP70 gene and susceptibility to occupational noise-induced hearing loss in Chinese Han workers exposed to noise and to analyze whether these 3 loci is the susceptibility biomarkers of occupational noise- induced hearing loss and to provide the theoretical basis for the primary prevention and screening the susceptible individuals. MethodsUsing the method of case-control studies, 3790 workers exposed to noise in a steel factory of Henan province in china participated in this study. According to the criterion that excluding of non noise-induced hearing loss, the average of binaural hearing threshold level of high frequency(3000Hz, 4000 Hz, 6000Hz) is greater than or equal to 40 d B or on the basis of this, the average of single hearing threshold level of low frequency(500Hz, 1000 Hz, 2000Hz) is greater than or equal to 26 d B, 297 cases were included. 297 controls was got according the matched criterion that the same gender, the same type of work, difference of age no more than five years old and difference of exposure to noise no more than 2 years. Genomic DNA was obtained from peripheral blood samples according to using 2ml DNA extraction Kit(Life Feng, Shanghai, China).An SNPscanTM multiplex SNP genotyping kit(Tian Hao, Shanghai, China)was employed to detect genotypes of these three loci among 594 samples. Using Epi Data3.0 software built library and managed data, SPSS13.0 software for statistical analysis. Using chi-square test to assess whether there were differences in the distribution of categorical variables between the case group and the control group. Using t test to assess whether there were differences in the quantitative data between the case group and the control group. Hardy Weinberg equilibrium was analysed using IHG on-line software(http://ihg.gsf.de/cgi-bin/hw/hwa1.pl). Haplotype was analysed using R software. The influence factors of susceptibility of noise-induced hearing loss and gene-environment interaction were analysed using conditional logistic regression. ResultsThe difference of distribution of genotype CC, TC, TT in rs2763979 locus of HSP70 gene between the case group and the control group was statistically significant(P < 0.05). Conditional logistic regression analysis showed that genotype TT in rs2763979 locus of HSP70 gene was risk factor for noise-induced hearing loss(OR=1.993, 95%CI: 1.043-3.808), while rs1043618 and rs2075800 loci of HSP70 gene were not associated with noise-induced hearing loss. Smoking was risk factor for noise-induced hearing loss(OR=1.756, 95%CI: 1.176-2.621). It was also showed that smoking and TT genotype of rs2763979 loci existed interaction. Using R software analysis found that after adjusting confounding factors such as smoking and drinking, haplotype CCT(OR = 1.43, 95% CI: 1.05-1.94) and GCT(OR = 1.52, 95% CI: 1.02-2.28) were risk factors for noise-induced hearing loss. ConclusionRs2763979 locus of HSP70 gene was associated with the susceptibility of noise-induced hearing loss, whose genotype TT was a risk factor for noise-induced hearing loss. Smoking was a risk factor for noise-induced hearing loss and smoking and TT genotype of rs2763979 loci existed interaction. Haplotype CCT and GCT were also risk factors for noise-induced hearing loss.