Genetic Variation in POU4F3 and GRHL2 Associated with Noise-Induced Hearing Loss in Chinese Population: A Case-Control Study.

Noise-induced hearing loss (NIHL) is an important occupational disease worldwide resulting from interactions between genetic and environmental factors. The purpose of this study was to examine whether genetic variations in POU4F3 and GRHL2 may influence susceptibility to NIHL in the Chinese population. A matched case-control study was carried out among 293 hearing loss individuals and 293 normal hearing workers drawn from a population of 3790 noise-exposed workers. Ten single-nucleotide polymorphisms (SNPs) in POU4F3 and GRHL2 were selected and genotyped. Logistic regression was performed to analyze the main effects of SNPs and the interactions between noise exposure and SNPs. Moreover, the interactions between predictor haplotypes and noise exposure were also analyzed. Analysis revealed that the CC genotype of rs1981361 in the GRHL2 gene was associated with a higher risk of NIHL (adjusted OR = 1.59; 95% CI: 1.08-2.32, p = 0.018). Additionally, the GG genotype of rs3735715 in the GRHL2 gene was also a risk genotype (adjusted OR = 1.48; 95% CI: 1.01-2.19, p = 0.046). Significant interactions were found between rs3735715, rs1981361 (GRHL2), rs1368402 as well as rs891969 (POU4F3) and noise exposure in the high-level exposure groups. Furthermore, the protective haplotype CA in the POU4F3 gene and the risk haplotype GCCG in the GRHL2 gene were identified combined with noise exposure. These results indicated that GRHL2 might be an NIHL susceptibility gene, but the effect of POU4F3 on NIHL could only be detected when taking noise exposure into account, and their effects were enhanced by higher levels of noise exposure. However, the differences were not significant after the Bonferroni correction was applied. These results should be seen as suggestive.