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.

Long Miao,Boshen Wang,Lihong Yin,Juan Zhang,Yuepu Pu

doi:10.1007/s11356-021-13649-4

Abstract

The purposes of the current study were to investigate the association of a few of 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. Plasmid construction, cell transfection, and dual-luciferase reporter assay were performed to investigate the potential molecular mechanism of SNPs involving in NIHL. The results revealed that 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), when GG genotype as a reference. Furthermore, the haplotype TCCTACT (rs2304186-rs41275750-rs76524493) was found to be significantly associated with a high risk of NIHL (OR = 1.19; 95% CI = 1.02-1.40). Functional experiments showed that rs2304186 G allele combined with hsa-miR-625-5p mimics could significantly decrease the luciferase activity compared with T allele, indicating that rs2304186 altered the binding affinity of hsa-miR-625-5p to SNP rs2304186 mutation region, thus directly targeting AKT2 gene. In conclusion, our study provides evidence for the first time that SNP rs2304186 of AKT2 3'UTR might affect NIHL susceptibility by altering the binding affinity of has-miR-625-5p to mutation region in an allele-specific manner and it may act as a potential biomarker of NIHL susceptibility.

Highlights

Occupational noise is known as a common harmful factor affecting workers' health in occupational health field
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
We found the rs2304186 GT/TT conferred a higher risk for NIHL in noise exposure time > 16 years group and noise exposure level > 92 dB group, suggesting long period and highlevel noise exposure combined with SNP rs2304186 of AKT2 could contribute to a higher NIHL risk

Summary

Introduction

Occupational noise is known as a common harmful factor affecting workers' health in occupational health field. Noise-induced hearing loss (NIHL) has become the second leading form of progressive sensorineural hearing defect caused by occupational noise exposure, after age-related hearing impairment (Miao et al 2019). NIHL is the most common occupation-related hearing defect and is an urgent public health issue around the world. The World Health Organization (WHO) previously reported that approximately 10% of population worldwide are exposed to high-intensity noise level environment and may develop NIHL (Basner et al 2014). The previous study found that 16% of adult disabling hearing loss worldwide can be attributed to occupational noise, accounting for 4.1 million disability-adjusted life years (DALYs) (Nelson et al 2005). In China, NIHL has become the third largest occupational health hazard, accounting for about one-sixth of the annual increase in occupational related-illnesses (Yu 2016)

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