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Association between UBAC2 gene polymorphism and the risk of noise-induced hearing loss: a cross-sectional study

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Abstract

The purpose of this article was to investigate the association between the ubiquitin-associated domain-containing protein 2 (UBAC2) gene polymorphism and noise-induced hearing loss (NIHL) and to further explore the role of single-nucleotide polymorphism (SNP) in UBAC2 in NIHL. A case control study involving 660 NIHL cases and 581 controls was conducted in this research. After genotyping by multiplex polymerase chain reaction (PCR) with next-generation sequencing, the correlation between SNPs and NIHL was analyzed using logistic regression analysis. Haplotype analysis was performed by Haploview 4.1 software. Then luciferase reporter assays and siRNA were used to explore the mechanism of SNPs in UBAC2 affecting NIHL susceptibility. The correlation analysis showed that rs3825427 AA genotype, rs9517701 GG genotype, rs7999348 GG genotype, and rs2296860 AA genotype were all associated with increased risk of NIHL (P < 0.05). The haplotype AGGA (rs3825427-rs9517701-rs7999348-rs2296860) also had a higher risk of NIHL (OR = 1.314; 95% CI, 1.098–1.572; P = 0.003). The results of the luciferase reporter assays showed that the fluorescence intensity of CTCF-OE + UBAC2 WT + TK was significantly higher than that of CTCF-NC + UBAC2 WT + TK and CTCF-OE + UBAC2 MT + TK (all P < 0.01). In CTCF knockdown cells, the expression of UBAC2 was also significantly downregulated (P = 0.0038), indicating that the transcription factor CTCF positively regulated the expression of UBAC2 and the rs3825427 C allele acted as an enhancer, which can promote CTCF to bind to the promoter of UBAC2, thereby promoting transcription. UBAC2 gene polymorphism is related to NIHL susceptibility. The UBAC2 rs3825427 regulates the expression level of UBAC2 by affecting the combination of CTCF and DNA, thus affecting the susceptibility of NIHL.

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Funding

This study was supported by the Natural Science Foundation of Jiangsu Province [BK20201485]; the Key Program of Jiangsu Provincial Health and Health Commission Medical Research [K2019026]; and Jiangsu Province’s Outstanding Medical Academic Leader program [CXTDA2017029].

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Authors and Affiliations

  1. Jiangsu Provincial Center for Disease Prevention and Control, No.172 Jiangsu Road, Nanjing, 210009, Jiangsu, China

    Liu Wan, Ludi Zhang, Peng Sun, Lei Han, Hengdong Zhang, Baoli Zhu & Boshen Wang

  2. Key Laboratory of Environmental Medicine Engineering of Ministry of Education, School of Public Health, Southeast University, Nanjing, 210009, Jiangsu, China

    Liu Wan, Ludi Zhang, Peng Sun, Baoli Zhu & Boshen Wang

  3. Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, 210000, Jiangsu, China

    Baoli Zhu

  4. Institute of Occupational Disease Prevention, Jiangsu Provincial Center for Disease Control and Prevention, No.172 Jiangsu Road, Nanjing, Jiangsu, China

    Boshen Wang

Authors
  1. Liu Wan
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  2. Ludi Zhang
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  3. Peng Sun
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  4. Lei Han
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Contributions

Liu Wan, Boshen Wang, Ludi Zhang, and Peng Sun: conceptualization, methodology, software, and writing—original draft preparation.

Lei Han and Hengdong Zhang: data curation and writing—original draft preparation.

Baoli Zhu: visualization and investigation.

Boshen Wang: data curation, investigation, and supervision.

Liu Wan and Boshen Wang: software, validation, and supervision.

Hengdong Zhang: writing—reviewing and editing.

Baoli Zhu: data curation and writing—reviewing and editing.

Corresponding authors

Correspondence to Baoli Zhu or Boshen Wang.

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Ethics approval

This research took into account the use of secondary data analysis. The patients’ private information was encrypted by the Jiangsu Provincial Centre for Disease Control and Prevention (CDC). In abiding with the ethical requirements, the study conformed to the Declaration of Helsinki and was nominated to be exempted from institutional ethical review by the Research Ethics Board of Jiangsu Provincial CDC.

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Official permission was taken from each respondent for this study, and informed consent was obtained from all participants.

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Consent was given by all contributing authors.

Competing interests

The authors declare no competing interests.

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Wan, L., Zhang, L., Sun, P. et al. Association between UBAC2 gene polymorphism and the risk of noise-induced hearing loss: a cross-sectional study. Environ Sci Pollut Res 29, 32947–32958 (2022). https://doi.org/10.1007/s11356-021-18360-y

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