SummaryMillions of people are daily exposed to high levels of noise. Consequently, noise-induced hearing loss (NIHL) is one of the most important occupational health hazards worldwide. In this study, we performed an association study for NIHL based on a candidate gene approach. 644 Single Nucleotide Polymorphisms (SNPs) in 53 candidate genes were analyzed in two independent NIHL sample sets, a Swedish set and part of a Polish set. Eight SNPs with promising results were selected and analysed in the remaining part of the Polish samples. One SNP in PCDH15 (rs7095441), resulted in significant associations in both sample sets while two SNPs in MYH14 (rs667907 and rs588035), resulted in significant associations in the Polish sample set and significant interactions with noise exposure level in the Swedish sample set. Calculation of odds ratios revealed a significant association of rs588035 with NIHL in the Swedish high noise exposure level group. Our studies suggest that PCDH15 and MYH14 may be NIHL susceptibility genes, but further replication in independent sample sets is mandatory.

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Noise-induced hearing loss (NIHL) is an important occupational hazard that results from an interaction between genetic and environmental factors. Although the environmental risk factors have been studied quite extensively, little is known about the genetic factors. On the basis of multiple studies, it was proposed that oxidative stress plays an important role in the development of NIHL. Here, we investigated whether variations (single nucleotide polymorphisms; SNPs) in the catalase gene (CAT), one of the genes involved in oxidative stress, influence noise susceptibility. Audiometric data from 1261 Swedish and 4500 Polish noise-exposed labourers were analysed. DNA samples were collected from the 10% most susceptible and the 10% most resistant individuals. Twelve SNPs were selected and genotyped. Subsequently, the interaction between noise exposure and genotypes and their effect on NIHL were analysed using logistic regression. Significant interactions were observed between noise exposure levels and genotypes of two SNPs for the Swedish population and of five SNPs for the Polish population. Two of these SNPs were significant in both populations. The interaction between predictor haplotypes and tagSNP haplotypes and noise exposure levels and their effect on NIHL were also analysed, resulting in several significant associations. In conclusion, this study identified significant associations between catalase SNPs and haplotypes and susceptibility to development of NIHL. These results indicate that catalase is a NIHL susceptibility gene, but that the effect of CAT polymorphisms can only be detected when noise exposure levels are taken into account.

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SummaryNoise-induced hearing loss (NIHL) is one of the leading occupational health risks in industrialized countries. It results from an interaction between environmental and genetic factors, however the nature of the genetic factors contributing to NIHL has not yet been clarified. Here, we investigated whether genetic variations in 10 genes putatively involved in the potassium recycling pathway in the inner ear may influence susceptibility to noise. 99 SNPs were genotyped in Polish noise-exposed workers, categorized into susceptible and resistant subjects. The most interesting results were obtained for KCNE1 and KCNQ4 as we replicated associations that were previously reported in a Swedish sample set, hence confirming that they are NIHL susceptibility genes. Additionally we report significant associations in GJB1, GJB2, GJB4, KCNJ10 and KCNQ1, however due to the lack of replication in the Swedish sample set, these results should be seen as suggestive.