DNMT1 and DNMT3A haplotypes associated with noise-induced hearing loss in Chinese workers

Enmin Ding,Haoran Guo,Hengdong Zhang,Wei Gong,Baoli Zhu,Huanxi Shen,Haiyan Song,Jing Liu

doi:10.1038/s41598-018-29648-4

Abstract

This study was conducted to explore the effects of DNMT1 and DNMT3A polymorphisms on susceptibility to noise-induced hearing loss (NIHL) in Chinese workers. A total of 2689 industrial workers from a single textile factory were recruited. Venous blood was collected, as were questionnaire and pure-tone audiometry (PTA) data by specialist physicians. Four selected SNPs (rs7578575, rs749131, rs1550117, and rs2228611) in DNMT1 and DNMT3A were genotyped in 527 NIHL patients and 527 controls. Then, main effects of the genotypes and their interactions were evaluated. Results revealed that the GG genotype at rs749131 and the AG/GG genotypes at rs1550117 and rs2228611 [odds ratio (OR) = 1.87, 2.57, and 1.98 respectively], as well as the haplotypes AGGG and TGGA (rs7578578-rs749131-rs1550117-rs2228611) (OR = 1.35 and 1.56, respectively) were associated with an increased risk of NIHL in the Chinese population. Multifactor dimensionality reduction analysis indicated that rs7578575, rs749131, and rs2228611 interact and are related to increased NIHL risk (OR = 1.63). The genetic polymorphisms rs749131 G, rs1550117 G, and rs2228611 G within the DNMT1 and DNMT3A genes are associated with an increased risk of NIHL in the Chinese population and have the potential to act as biomarkers for noise-exposed workers.

Highlights

Occupational noise is one of the most common occupational hazards affecting the health of industrial workers, and noise-induced hearing loss (NIHL) is the second most frequent form of sensorineural hearing impairment besides age-related hearing loss (ARHL) worldwide[1]
Considering the vital roles of DNA methyltransferase 1 (DNMT1) in hearing disorders and of DNMT3A in oxidative stress, we speculated that polymorphisms in DNMT1, DNMT3A and their interactions could be associated with genetic susceptibility to NIHL
General information for the selected single nucleotide polymorphisms (SNPs) and the results of Hardy-Weinberg tests are shown in Table 2. rs7578575 and rs749131 are located in DNMT3A introns, rs1550117 is located in the 2 kb region upstream of DNMT3A, and rs2228611 is a synonymous SNP in DNMT1

Summary

Introduction

Occupational noise is one of the most common occupational hazards affecting the health of industrial workers, and noise-induced hearing loss (NIHL) is the second most frequent form of sensorineural hearing impairment besides age-related hearing loss (ARHL) worldwide[1]. Previous studies have found that single nucleotide polymorphisms (SNPs) in the HSP70, EYA4, CDH23, GRHL2, and DFNA5 genes are associated with genetic susceptibility to NIHL in humans and may increase or decrease the risk of NIHL through interactions with occupational noise[9,10,11]. DNA methylation represses gene expression through the allosteric inhibition of transcription factors and the transcriptional machinery while serving as a recognition site for a host of repressive factors[12] This modification is applied by DNA methyltransferase (DNMT) proteins. Considering the vital roles of DNMT1 in hearing disorders and of DNMT3A in oxidative stress, we speculated that polymorphisms in DNMT1, DNMT3A and their interactions could be associated with genetic susceptibility to NIHL. We performed a case-control study to elucidate the associations between four DNMT1 and DNMT3A SNPs, namely rs7578575, rs749131, rs1550117, and rs2228611, and genetic susceptibility to NIHL

Methods

Results

Conclusion