title: Associations of genetic variations in EYA4, GRHL2 and DFNA5 with noise-induced hearing loss in Chinese population: a case- control study.
abstract: BACKGROUND
  Both environmental and genetic factors are attributable to the incidence of noise-induced hearing loss (NIHL). The purpose of this study was to examine the associations between genetic variations in the EYA4, GRHL2 and DFNA5 genes and the risk to noise-induced hearing loss (NIHL) in a Chinese population.
  
  
  METHODS
  A case-control study was conducted with 476 NIHL workers and 475 normal hearing workers matched with gender, years of noise exposure, and intensity of noise exposure. Twelve tag single-nucleotide polymorphisms (SNP) in the EYA4, GRHL2 and DFNA5 genes were genotyped using nanofluidic dynamic arrays on the Fluidigm platform. Multiple logistic regression was used to analyze the associations of genetic variations with NIHL adjusted by age, smoking/drinking status, and cumulative noise exposure and their interactions with noise exposure.
  
  
  RESULTS
  The SNPs of rs3777781and rs212769 in the EYA4 gene were significantly associated with NIHL risk. In rs3777781, comparing with the subjects carrying with TT types, the carriers with AT and AA genotypes had the decreased risk of NIHL (OR = 0.721, 95% CI = 0.522 - 0.996). In rs212769, the AG and AA carriers had increased NIHL risk (OR = 1.430, 95% CI = 1.014 - 2.016) compared with the subjects with GG genotype. Rs666026 in the associated GRHL2 gene and rs2521758 in the DFNA5 gene were marginally t associated with NIHL (P = 0.065 and 0.052, respectively). Rs2521758 and rs212769 had significantly interacted with noise exposure (P < 0.05).
  
  
  CONCLUSIONS
  Genetic variations in the EYA4, GRHL2 and DFNA5 genes and their interactions with occupational noise exposure may play an important role in the incidence of NIHL.
authors.affiliation: Hangzhou Center for Disease Control and Prevention, Hangzhou, 310021, P.R. China.
authors.forename: Xuhui
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Epidemiology and Biostatistics, Zhejiang University School of Public Health, 388 Yu-Hang-Tang Road, Hangzhou, 310058, Zhejiang, P.R. China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Hangzhou Center for Disease Control and Prevention, Hangzhou, 310021, P.R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Hangzhou Center for Disease Control and Prevention, Hangzhou, 310021, P.R. China.
authors.forename: Zhangping
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Hangzhou Center for Disease Control and Prevention, Hangzhou, 310021, P.R. China.
authors.forename: Luoxian
authors.initials: L
authors.lastname: Yang
authors.affiliation: Hangzhou Center for Disease Control and Prevention, Hangzhou, 310021, P.R. China.
authors.forename: Xuchu
authors.initials: X
authors.lastname: Wang
authors.affiliation: Hangzhou Center for Disease Control and Prevention, Hangzhou, 310021, P.R. China.
authors.forename: CaiXia
authors.initials: C
authors.lastname: Jiang
authors.affiliation: Hangzhou Center for Disease Control and Prevention, Hangzhou, 310021, P.R. China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Hangzhou Center for Disease Control and Prevention, Hangzhou, 310021, P.R. China.
authors.forename: Yuyong
authors.initials: Y
authors.lastname: Xia
authors.affiliation: Hangzhou Hospital for Prevention and Treatment of Occupational Diseases, Hangzhou, 310014, Zhejiang, P.R. China.
authors.forename: Yanjuan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Hangzhou Center for Disease Control and Prevention, Hangzhou, 310021, P.R. China.
authors.forename: Ou
authors.initials: O
authors.lastname: Wu
authors.affiliation: Department of Epidemiology and Biostatistics, Zhejiang University School of Public Health, 388 Yu-Hang-Tang Road, Hangzhou, 310058, Zhejiang, P.R. China. zhuym@zju.edu.cn.
authors.forename: Yimin
authors.initials: Y
authors.lastname: Zhu
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D002681:China; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D004781:Environmental Exposure; D006317:Hearing Loss, Noise-Induced / Q000453:epidemiology* / Q000235:genetics; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009622:Noise / Q000009:adverse effects*; D020641:Polymorphism, Single Nucleotide; D011960:Receptors, Estrogen / Q000235:genetics* / Q000378:metabolism; D012306:Risk; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D055815:Young Adult; D000094524:Gasdermins
chemical_list: D004268:DNA-Binding Proteins; D011960:Receptors, Estrogen; D015534:Trans-Activators; D014157:Transcription Factors; C117736:EYA4 protein, human; C470830:GRHL2 protein, human; C111432:GSDME protein, human; D000094524:Gasdermins