A missense variant rs2585405 in clock gene PER1 is associated with the increased risk of noise-induced hearing loss in a Chinese occupational population

Abstract

Abstract Objective To investigate the potential association of cochlear clock genes (CRY1, CRY2, PER1, and PER2), the DNF gene (brain-derived neurotrophic factor), and the NTF3 gene (neurotrophin3) with susceptivity to noise-induced hearing loss (NIHL) among Chinese noise-exposed workers. Methods A nested case–control study was performed with 2056 noise-exposed workers from a chemical fiber factory and an energy company who underwent occupational health examinations in 2019 as study subjects. Propensity score matching was conducted to screen cases and controls by matching sex, age, and the consumption of tobacco and alcohol. A total of 1269 participants were enrolled. Then, general information and noise exposure of the study subjects were obtained through a questionnaire survey and on-site noise detection. According to the results of audiological evaluations, the participants were divided into the case group (n = 432, high-frequency threshold shift > 25 dB) and the matched control group (n = 837, high-frequency threshold shift ≤ 25 dB) by propensity score matching. Genotyping for PER1 rs2253820 and rs2585405; PER2 rs56386336 and rs934945; CRY1 rs1056560 and rs3809236; CRY2 rs2292910 and rs6798; BDNF rs11030099, rs7124442 and rs6265; and NTF3 rs1805149 was conducted using the TaqMan-PCR technique. Results In the dominant model and the co-dominant model, the distribution of PER1 rs2585405 genotypes between the case group and the control group was significantly different (P = 0.03, P = 0.01). The NIHL risk of the subjects with the GC genotype was 1.41 times the risk of those carrying the GG genotype (95% confidence interval (CI) of odds ratio (OR): 1.01–1.96), and the NIHL risk of the subjects with the CC genotype was 0.93 times the risk of those carrying the GG genotype (95%CI of OR: 0.71–1.21). After the noise exposure period and noise exposure intensities were stratified, in the co-dominant model, the adjusted OR values for noise intensities of ≤ 85 was 1.23 (95%CI: 0.99–1.53). In the dominant model, the adjusted OR values for noise exposure periods of ≤ 16 years and noise intensities of ≤ 85 were 1.88 (95%CI: 1.03–3.42) and 1.64 (95%CI: 1.12–2.38), respectively. Conclusion The CC/CG genotype of rs2585405 in the PER1 gene was identified as a potential risk factor for NIHL in Chinese noise-exposed workers, and interaction between rs2585405 and high temperature was found to be associated with NIHL risk.

Keywords

• Cochlear clock genes
• PER1
• Polymorphism
• Noise-induced hearing loss
• Susceptibility