Abstract
This study aimed to explore the association of several single nucleotide polymorphisms (SNPs) within the AKT2 gene and noise-induced hearing loss (NIHL) susceptibility and explore the potential mechanism underlying NIHL. Three SNPs (rs2304186, rs41275750 and rs76524493) were genotyped in a Chinese population which consists of 690 NIHL patients and 650 normal hearing controls. Bioinformatic analysis was conducted to predict the potential miRNA-binding site of SNPs. Cell transfection and dual-luciferase reporter assay were performed to investigate the potential molecular mechanism of SNPs involved in NIHL. The results revealed rs2304186 GT genotype (OR = 1.41; 95% CI = 1.09–1.83) and TT genotype (OR = 1.51; 95% CI = 1.08–2.10) imparted increased risk of NIHL, and the increased risk could also be found in a dominant model (OR = 1.44; 95% CI = 1.12–1.84). The stratification analysis showed that rs2304186 GT/TT conferred a higher risk for NIHL, especially in subgroups of male, age (35–45 and > 45 years), noise exposure time (> 16 years), and noise exposure level (≤ 85 and ≥ 92 dB), compared with GG genotype. In addition, the haplotype TCCTACT (rs2304186-rs41275750-rs76524493) was associated with NIHL risk (OR = 1.19; 95% CI = 1.02–1.40). Rs2304186 G allele combined with hsa-miR-625-5p mimics could significantly decrease the luciferase activity compared with T allele, indicating rs2304186 altered the binding affinity of hsa-miR-625-5p to SNP rs2304186 mutation region, thus directly targeting AKT2. In conclusion, our study provides evidence for the first time that SNP rs2304186 of AKT2 3′UTR affects NIHL susceptibility by affecting the binding affinity of has-miR-625-5p in an allele-specific manner and it may act as a potential biomarker of NIHL susceptibility.
A functional SNP in miR-625-5p binding site of AKT2 3′UTR is associated with noise-induced hearing loss susceptibility in the Chinese population
