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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

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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.

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Data availability

The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

The authors thank every worker for their participations in this study.

Funding

This study was supported by the Open Research Fund of State Key Laboratory of Bioelectronics, Southeast University.

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Author notes

  1. Long Miao and Boshen Wang contributed equally to this work.

Authors and Affiliations

  1. Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nan**g, 210009, People’s Republic of China

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

Authors
  1. Long Miao
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  2. Boshen Wang
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  3. Juan Zhang
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  4. Lihong Yin
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  5. Yuepu Pu
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Contributions

YP designed the research study. LM and BW performed the research and analyzed the data. LM drafted the manuscript. JZ and LY critically reviewed and revised the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Yuepu Pu.

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Ethics approval and consent to participate

The present study was approved by the Ethics Committee of Zhongda Hospital, Affiliated Hospital of Southeast University.

Informed consent was obtained from all individual participants included in the study.

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The participant has consented to the submission of the case report to the journal.

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The authors declare no competing interests.

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Responsible Editor: Lotfi Aleya

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Miao, L., Wang, B., Zhang, J. et al. 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. Environ Sci Pollut Res 28, 40782–40792 (2021). https://doi.org/10.1007/s11356-021-13649-4

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