Noise-induced hearing loss (NIHL) is one of the most common occupational health risks in industrialized countries. It has been recognized to result from interactions between genetic and environmental factors. This study investigated the influence of genetic mutations in the potassium voltage-gated channel subfamily E regulatory subunit 1 (KCNE1) gene on susceptibility to NIHL. A total of 2689 industrial workers in eastern China were recruited to participate. Three single-nucleotide polymorphisms (SNPs) of KCNE1 were genotyped in noise-exposed workers who were classified into 589 cases and 639 control individuals. Then, main effects of the genotypes and their interactions with environmental factors were evaluated. Results showed that the rs3453 C allele located in KCNE1 3'-UTR region and the rs1805127 G allele in the encoding region were associated with increased risk of NIHL in the Chinese population. There is an association between TAA, TAG, and other (CAA/CGA) haplotypes (rs3453-rs11702354-rs1805127) and increased risk of NIHL with OR = 1.33, 1.43, and 2.93 (P = 0.022, 0.017, and 0.001 respectively) compared with CGG group. Results also showed a significant interaction between rs3453, rs1805127, and high-temperature exposure (P = 0.0002, adjusted OR = 1.85). The cellular evidence indicated that polymorphisms rs3453 and rs1805127 may play key roles in hearing loss through affecting KCNE1 expressions by the way of microRNA and protein respectively. The further animal study is still needed to confirm these mechanisms. KCNE1 rs3453 and rs1805127 may have a potential as biomarkers for screening the susceptibility to NIHL.
Keywords: Association study; Genetic study; Haplotype; KCNE1; Noise-induced hearing loss; Polymorphism.