Identification of functional tag single nucleotide polmorphisms within the entire CAT gene and their clinical relevance in patients with noise-induced hearing loss

摘要

Objectives: Noise-induced hearing loss (NIHL) is an important occupational disease which results from an interaction between genetic and environmental factors. More and more evidences suggested that Catalase (CAT) gene polymorphism plays an important role in the development of NIHL. The aim of this study was to investigate the association of CAT gene polymorphisms with NIHL in a case-control study. Design: A total of 719 unrelated adult Chinese Han population, including 225 healthy volunteers and 494 noise-exposed workers were recruited in this study. Six tag single-nucleotide polymorphisms (tSNPs) were genotyped using an improved multiplex ligation detection reaction technique. Subsequently, the interaction between noise exposure level and genotypes and their effect on NIHL were analyzed using logistic regression. Results: Among six tSNPs, two of them (rs208679 and rs769217) were significantly associated with noise exposure level. For rs208679 recessive effect, GG genotype had a significantly increased of NIHL risk in the exposure level of < 85 dB; and for rs769217 dominant effect, the combined genotypes TT/TC had a significantly increased of NIHL risk in the exposure level of 85 dB~92 dB; and the haplotype A-G-T-C-A-C had a risk effect on the NIHL in the exposure level of 85 dB~92 dB. In addition, the rs769217 polymorphism could enhance the transcription activities of the CAT gene. Conclusions: This study identified CAT is a NIHL susceptibility gene when noise exposure levels are taken into account. Rs208679 and rs769217 polymorphisms might be used as relevant risk estimates for the development of NIHL in population with different noise exposure levels.