关键词:  GRHL2, 多态现象, 遗传, 听觉丧失, 噪声性, 疾病易感性

Abstract:

Objective： To investigate association between genetic polymorphism in the grainyhead-like 2 gene (GRHL2) and noise-induced hearing loss (NIHL) in the Chinese population. Methods: A matched case-control association study was employed, In which, 3 790 workers exposed to continuous and steady-state occupational noise in a steel factory participated. The questionnaires were adopted to collect individual features and audiometry tests performed. In the sstudy, 286 subjects were diagnosed as cases, Which were each designated on the basis of the matched criterion, and 286 paired samples were selected finally. Noise intensity was measured according to the standards given in ‘Measurement of Noise in the Workplace’(Occupational Health Standard of the People’s Republic of China, GBZ/T189.8-2007). Cumulative noise exposure (CNE) was calculated, according to monitoring data on A-weighed sound pressure level and employment time. Genomic DNA was obtained from peripheral blood samples using 2 mL DNA extraction Kit following the manufacturer’s protocol. Five single nucleotide polymorphisms (SNPs) of GRHL2 were genotyped by multiplex SNP genotyping kit. The continuous variables and categorical variables were analyzed by t-test and chi-square test respectively. Multivariate Logistic regression was used to test the association between genetic frequency and disease status, with adjustments for the possible confounding variables. The haplotypes were established and their frequencies in the two groups were assessed by haploview and phase softwares. Results: All the five SNPs (rs3735713, rs3824090, rs3735714, rs3735715 and rs611419) were in Hardy-Weinberg equilibrium (HWE) (P>0.05). The subjects carrying rs3735715 GG genotype had a higher NIHL risk than those carrying the GA genotype under the co-dominant model (OR=0.644, 95% CI: 0.442－0.939, P=0.022) after adjustment for height, blood pressure, drinking status and smoking status. After being stratified by CNE, in the CNE ≥ 98 dB (A) group, rs3735715 polymorphism was associated with the NIHL under the co-dominant model (OR=0.509, 95% CI: 0.281－0.923, P=0.026) after adjustment for height, blood pressure, drinking status and smoking status as well. However, no statistical significant difference was found in variant genotypes of the other SNPs between the case and control subjects. Four-locus (rs3735713, rs3824090, rs3735714 and rs3735715) haplotypes were constructed, and no risk or protective haplotypes was identified. Conclusion: It is suggested that GRHL2 polymorphisms may be associated with development of NIHL.

Key words: GRHL2, Polymorphism, genetic, Hearing loss, noise-induced, Disease susceptibility