Assessment And Preliminary Validation Of Genetic Risk On Noise Induced Hearing Loss

Backgrounds and ObjectivesNoise exposure,one of the most common occupational risk factors,may cause many harmful effects on health,including irritability,insomnia,fatigue,hearing loss and other symptoms.Researches showed that noise hearing loss?NIHL?is a complex disease affected by environmental factors and genetic factors.Previous findings indicated that people exposed similar noise environment could have different degrees of NIHL risk,which means that NIHL had individual susceptibility.Researchers had done a lot of studies on NIHL susceptibility genes,the possible susceptibility genes mainly include:oxidative stress genes,potassium-recycling pathway genes,monogenic deafness genes,Hsp70 genes,and DNA damage repair genes.However,the genetic mechanisms of NIHL pathogenesis still remains uncovered.Previous studies always used a single gene,and a few SNPs to study NIHL susceptibility,and their study sample size was generally small.Firstly,we conducted a case-control study with 476 NIHL workers and 475 normal hearing workers.We used nanofluidic dynamic arrays on the Fluidigm platform to genotype 93 SNPs in 32 genes.And we found 14 SNPs associated with NIHL.But the effect of a single polymorphism loci is week,so in this study we design to preliminary establish NIHL risk prediction models to screen for NIHL high-risk groups on the basis of 14 SNPs,and analyze the interaction between environmental factors and genetic factors.At last,to validate these SNPs and NIHL risk prediction models in a cohort study.Material and MethodsThe subjects were recruited from a cross-sectional survey conducted between 2011 and 2012,the workers were employed in the noise-exposed factories of mechanical equipment and household appliance manufacturing,steel construction,and cigarette production packaging in Hangzhou,Zhejiang province.According to a certain screening criteria,476 NIHL cases and 475 healthy controls were obtained.We used C-GRS and W-GRS to calculate genetic risk score,the subjects were grouped by individual score,and we used unconditional logistic regression to analyze the correlation between GRS and NIHL.Then we used crossover analysis to explore the interaction effects between environment factors and GRS.Removed the workers who had already happened to NIHL,the subjects were followed up in 2016.According to C-GRS and W-GRS scores,the subjects were divided into high and low groups,and then we calculate the incidence of NIHL in different genotype and different GRS groups.We used unconditional logistic regression to calculate OR and 95%CI,and we calculate Relative Risk?RR?according to the equation:Relative Risk =OR/??1-P₀?+?P₀ ×OR??.We also used Kruskal-Wallis H test to analyse the change of Binaural hf listening threshold between the subjects with different genotype.ResultsWe used C-GRS and W-GRS to establish NIHL risk prediction models,and we found that the incidence of NIHL was positively correlated with the increase of the number of risk alleles with statistical significance?Ptrend<0.001?.Compared with the individuals C-GRS<10,the individuals C-GRS>10 had a 2.689-fold risk of NIHL?OR=2.689,95%CI:1.707-4.234,P<0.001?,and compared with the individuals W-GRS<3.9,the individuals C-GRS>3.9 had a 2.986-fold risk of NIHL?OR=2.986,95%CI:1.938-4.601,P<0.001?.Analysis of the interaction between GRS and environmental factors found that there are interaction effects between GRS and smoking?P=0.023?.Although we did not find interaction effect between GRS and noise intensity,CNE and drinking,but the NIHL prevalence rates of high GRS were significantly higher than those of low GRS and its risk had increased trend?Ptrend<0.05?.In the cohort,we validated the following SNPs:rs212769 and rs7910544.The results of GRS risk prediction models were not statistically significant,but there is a rising trend of the incidence of NIHL with the increase of C-GRS and W-GRS.ConclusionOur study preliminary established NIHL risk prediction models to screening for NIHL high-risk groups on the basis of 14 SNPs,and we found that the incidence of NIHL was positively correlated with the increase of the number of risk alleles.Analysis of the interaction between GRS and environmental factors found that there are interaction effects between GRS and smoking.In the cohort,we validated the SNPs of rs212769 and rs7910544.The results of GRS risk prediction model were not statistically significant in the cohort study,but there is a rising trend of the incidence of NIHL with the increase of C-GRS and W-GRS.