Polymorphisms of heat shock protein 70 genes (HSPA1A, HSPA1B and HSPA1L) and susceptibility of noise-induced hearing loss in a Chinese population: A case-control study

PLOS ONE, Dec 2019

Noise-induced hearing loss (NIHL) is the second-most frequent form of sensorineural hearing loss. When exposed to the same noise, some workers develop NIHL while others do not, suggesting that NIHL may be associated with genetic factors. To explore the relationship between single nucleotide polymorphisms (SNPs) in heat shock protein 70 (HSP70) genes (HSPA1A, HSPA1B and HSPA1L) and susceptibility to NIHL in Han Chinese workers exposed to noise, a case-control association study was carried out with 286 hearing loss cases and 286 matched with gender, age, type of work, and exposure time, drawn from a population of 3790 noise-exposed workers. Four SNPs were selected and genotyped. Subsequently, the effects of the alleles and genotypes of the three HSP70 genes (HSPA1A, HSPA1B and HSPA1L) on NIHL were analyzed by using a conditional logistic regression. A generalized multiple dimensionality reduction (GMDR) was applied to further detect an interaction between the four SNPs. Compared with the combined genotypes CC/TC, carriers of the TT genotype of rs2763979 appeared to show greater susceptibility to NIHL (P = 0.042, adjusted OR = 1.731, 95% CI 1.021–2.935). A significant interaction between rs2763979 and CNE was found (P = 0.029), and a significant association was found between TT of s2763979 and NIHL (P = 0.024, adjusted OR = 5.694, 95%CI 1.256-25.817) in the 96 dB (A)≤CNE<101 dB (A) group. The results suggest that the rs2763979 locus of the HSP70 genes may be associated with susceptibility to NIHL in Chinese individuals, and other HSP70 genes may also be susceptibility genes for NIHL, but the results must be further replicated in additional independent sample sets.

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Polymorphisms of heat shock protein 70 genes (HSPA1A, HSPA1B and HSPA1L) and susceptibility of noise-induced hearing loss in a Chinese population: A case-control study

February Polymorphisms of heat shock protein 70 genes (HSPA1A, HSPA1B and HSPA1L) and susceptibility of noise-induced hearing loss in a Chinese population: A case-control study Yanhong Li 0 1 Shanfa Yu 0 1 Guizhen Gu 0 1 Guoshun Chen 1 Yuxin Zheng 1 Jie Jiao 0 1 Wenhui Zhou 0 1 Hui Wu 0 1 Zengrui Zhang 0 1 Huanling Zhang 1 Lihua He 1 Qiuyue Yang 1 Xiangrong Xu 1 0 Henan Provincial Institute for Occupational Health , Zhengzhou , People's Republic of China, 2 Wugang Institute for Occupational Health , Wugang , People's Republic of China, 3 National Institute of Occupational Health and Poison Control, Chinese Center for Disease Control and Prevention , Beijing , People's Republic of China, 4 Department of Occupational Health and Environmental Health, School of Public Health, Peking University , Beijing , People's Republic of China 1 Editor: Qingyi Wei, Duke Cancer Institute , UNITED STATES - Data availability statement: All relevant data are within the paper and its Supporting Information files. Introduction Noise-induced hearing loss (NIHL) is caused by regular exposure to continuous noise or exposure to a single acoustic overstimulation. Since the industrial revolution, an increasing number of people are exposed on a daily basis to harmful levels of noise in their work environment. As a result, NIHL is the second-most common form of sensorineural hearing loss after presbycusis [ 1 ]. Thirty-five million people are at risk for developing NIHL in Europe alone [ 2 ]. Ten million people in the United States have noise-related hearing loss, and the number of workers in China with NIHL has increased 77.8% in the past three years (2010±2012) [ 3 ]. NIHL is a complex disease caused by a combination of environmental and genetic factors. Noise >85 dB is harmful and causes both mechanical and metabolic damage [ 4 ]. Workers who are occupationally exposed to high levels of noise possess high rates of NIHL [ 5 ]. In addition, individual factors such as smoking, high blood pressure and cholesterol levels may influence the susceptibility to noise [ 5,6,7,8,9 ]. Not all workers exposed to the same levels and duration of noise will develop NIHL, and the degree of hearing loss varies widely, indicating that NIHL may be associated with genetic factors. Association studies have identified GSTM1, GSTT1, SOD1, SOD2, KCNE1, PON2, CAT, CDH23 and HSP70 as putative NIHL susceptibility genes [ 8,10,11,12,13,14,15,16,17 ]. However, some studies involving other populations found no significant association between NIHL and GSTM1, GSTT1 or SOD2 [ 18,19 ]. Heat-shock proteins (HSPs) that perform housekeeping and quality control functions in the cell [ 20 ] are expressed ubiquitously in cells under both physiological and pathological circumstances. The human HSP70 family is composed of three genes: HSPA1A, HSPA1B and HSPA1L [ 21 ]. All three are expressed in the cochlea after acoustic overstimulation [ 22 ]. In this study, we investigated whether we could replicate the associations observed between the single nucleotide polymorphisms (SNPs) in the HSP70 genes (HSPA1A, HSPA1B and HSPA1L) and susceptibility to NIHL in Han Chinese workers exposed to noise. Materials and methods Samples A total of 3790 Han workers exposed to continuous and steady-state occupational noise in a steel factory in the Henan province of China participated in this study. Cases and controls were selected as follows. First, according to the criterion that the average binaural hearing threshold level (HTL) to high frequency (3000 Hz, 4000 Hz and 6000 Hz) is greater than or equal to 40 dB or the average of single hearing threshold level to linguistic frequency (500 Hz, 1000 Hz and 2000 Hz) is greater than or equal to 26 dB, 479 cases were included from the 3790 subjects, and 958 controls who were frequency-matched by gender, age, type of work, and exposure time were also included from the remaining 3311 subjects. Second, 6 cases with no blood samples and their 12 controls were excluded. Third, an inclusion criterion for this study was an exposure to occupational noise higher than 80 dB(A) for more than 3 years. Subjects with a history of explosive noise exposure, skull trauma, contagious diseases (mumps, measles or rubella), middle ear disease, Meniere's disease, treatment with an ototoxic drug, perforated eardrum, or with a family history of hearing loss and subjects of non-noise-induced hearing loss were excluded. Additionally, controls with the average of binaural HTL of high frequency 35 dB or unilateral HL of any linguistic frequency >25 dB were excluded, including 6 cases and 18 controls whose noise exposure time was less than 3 years, 9 cases and 11 controls with a history of exposure to explosive noise, 5 cases and 6 controls with a history of skull trauma, 68 cases and 132 controls with a history of mumps, 9 cases and 17 controls with a history of 2 / 12 measles, 24 cases and 67 controls with a history of middle ear disease, 3 ca (...truncated)


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Yanhong Li, Shanfa Yu, Guizhen Gu, Guoshun Chen, Yuxin Zheng, Jie Jiao, Wenhui Zhou, Hui Wu, Zengrui Zhang, Huanling Zhang, Lihua He, Qiuyue Yang, Xiangrong Xu. Polymorphisms of heat shock protein 70 genes (HSPA1A, HSPA1B and HSPA1L) and susceptibility of noise-induced hearing loss in a Chinese population: A case-control study, PLOS ONE, 2017, Volume 12, Issue 2, DOI: 10.1371/journal.pone.0171722