[Association of DNMT3a's single nucleotide polymorphisms with susceptibility to noise-induced hearing loss in Chinese workers].

OBJECTIVE: To investigate the potential association of DNMT3a's single nucleotide polymorphism with susceptibility to noise-induced hearing loss( NIHL) in Chinese noise-exposed workers. METHODS: A case-control study was performed, and 998 noise-exposed workers from a chemical fibre factory and an energy company, who underwent occupational health examination in 2015, were enrolled as study subjects. Then, general information and noise exposure of the study subjects were obtained through questionnaire survey and on-site noise detection. According to the result of audiological evaluation, they were divided into case group( n = 498, high-frequency threshold shift >25 dB) and man-matched control group( n = 500, high-frequency threshold shift ≤25 dB). At last, genotyping of DNMT3a rs7590760 was conducted with TaqMan-PCR technique. RESULTS: In the dominant model, the distribution of rs7590760 genotypes between the case group and the control group was statistically significant( P = 0. 001). The NIHL risk of subjects with CC/CG genotype is 1. 56 times the risk of those carrying GG genotype, with an adjusted OR = 1. 56( 95% CI 1. 22-2. 01). After the noise exposure period and noise exposure intensity were stratified, the adjusted OR values for noise exposure period ≤16 years, > 16 years and noise intensity ≤85, 86-92 and >92 dB were respectively 1. 67( 95% CI 1. 17-2. 38), 1. 52( 95% CI 1. 06-2. 17), 1. 56( 95% CI 1. 06-2. 30), 1. 67( 95% CI 0. 94-2. 99) and 1. 51( 95% CI 1. 01-2. 26). CONCLUSION: The CC/CG genotype of rs7590760 in DNMT3a gene is a potential risk factor for noise-induced hearing loss in Chinese noise-exposed workers.

Analysis of Polymorphisms Associated with Base Excision Repair in Patients Susceptible and Resistant to Noise-Induced Hearing Loss.

OBJECTIVE: Noise-induced hearing loss (NIHL) is one of the most common occupational health risks in both developed and industrialized countries. It occurs as a result of interactions between genetic and environmental factors. Nevertheless, inherited genetic factors contributing to NIHL are not well understood. Therefore, we aim to investigate whether genetic mutations in three important base excision repair genes (OGG1, APEX1, and XRCC1) may influence susceptibility to NIHL. METHODS: Three SNPs in OGG1, APEX1, and XRCC1 were genotyped from 1170 noise-exposed workers and were classified into 117 most susceptible and 117 most resistant individuals. RESULTS: Results showed that the rs1799782 TT genotype located in the XRCC1 coding region and rs1130409 GG/GT in the APEX1 coding region were associated with increased risk for NIHL in a Chinese population. Compared to the rs1799782 C allele frequency, the T allele frequency was increased in the sensitive group (adjusted OR = 1.51, 95%CI = 1.01 to 2.26, P = 0.043). The rs1130409 G allele frequency was also increased in the sensitive group compared to the resistant group (adjusted OR = 1.59, 95%CI = 1.10 to 2.31, P = 0.015). Moreover, rs1130409 and drinking had a statistically significant interaction (P = 0.0002), while rs1799782, rs1130409, and smoking also had a statistically significant interaction (P < 0.0001). CONCLUSIONS: XRCC1 rs1799782 and APEX1 rs1130409 may have potential as biomarkers for the screening of susceptibility to NIHL in workers exposed severe noise.

Genetic variation in KCNQ4 gene is associated with susceptibility to noise-induced hearing loss in a Chinese population.

Noise-induced hearing loss (NIHL), one of the most widespread occupational health risks worldwide, is a kind of complex disorder resulting from both genetic and environmental factors. KCNQ4 channels are crucial to the internal ear potassium recycling. To explore whether KCNQ4 polymorphism is associated with individual susceptibility to NIHL, we performed this genetic association study on 571 NIHL cases and 639 normal hearing controls selected from about 2700 Chinese noise-exposed workers. General information and audiometric data were obtained through questionnaires and pure-tone audiometry (PTA). DNA samples were collected and genotyping for three selected SNPs (rs709688, rs2769256 and rs4660468) was performed. Significant differences were observed between cases and controls for the genotype frequency and allele frequency in rs4660468, suggesting that rs4660468 CT/TT genotype and T allele may be risk factors for NIHL. In subjects exposed to noise for more than 16 years (OR = 1.23, 95% CI = 1.09-1.53) and those who exposed to noise >92 dB (OR = 1.29, 95% CI = 1.08-1.69), increased risks of NIHL were found after stratified analysis for rs4660468. Our results suggest that rs4660468 T allele of KCNQ4 involves with a higher risk of NIHL and could be one biomarker of susceptibility for Chinese noise exposed workers.