NRN1 and CAT Gene Polymorphisms, Complex Noise, and Lifestyles interactively Affect the Risk of Noise-induced Hearing Loss

Objective The effects of interactions between genetic and environmental factors on the noise-induced hearing loss(NIHL)are still unclear.This study aimed to assess interactions among gene polymorphisms,noise metrics,and lifestyles on the risk of NIHL.Methods A case-control study was conducted using 307 patients with NIHL and 307 matched healthy individuals from five manufacturing industries.General demographic data,lifestyle details,and noise exposure levels were recorded.The Kompetitive allele-specific polymerase chain reaction(KASP)was used to analyze the genotypes of 18 SNPs.Results GMDR model demonstrated a relevant interaction between NRN1 rs3805789 and CAT rs7943316(P=0.0107).Subjects with T allele of rs3805789 or T allele of rs7943316 had higher risks of NIHL than those with the SNP pair of rs3805789-CC and rs7943316-AA(P<0.05).There was an interaction among rs3805789,rs7943316,and kurtosis(P=0.0010).Subjects exposed to complex noise and carrying both rs3805789-CT and rs7943316-TT or rs3805789-CT/TT and rs7943316-AA had higher risks of NIHL than those exposed to steady noise and carrying both rs3805789-CC and rs7943316-AA(P<0.05).The best six-locus model involving NRN1 rs3805789,CAT rs7943316,smoking,video volume,physical exercise,and working pressure for the risk of NIHL was found to be the interaction(P=0.0010).An interaction was also found among smoking,video volume,physical exercise,working pressure,and kurtosis(P=0.0107).Conclusion Concurrence of NRN1 and CAT constitutes a genetic risk factor for NIHL.Complex noise exposure significantly increases the risk of NIHL in subjects with a high genetic risk score.Interactions between genes and lifestyles as well as noise metrics and lifestyles affect the risk of NIHL.