Associations Of XYLT1 Gene Polymorphisms And The Onset Of Noise-induced Hearing Loss In A Chinese Population

Noise-induced hearing loss(NIHL)is also called occupational noise or occupational deafness.It refers to the long-term accumul ation of sensorineural deafness due to long-term exposure to noise.According to the "Classification and Catalogue of Occupational Diseases," there are 10 categories of statutory occupational diseases in China,with as many as 132 types,and the number of occupational hearing impairments has long been ranked in the top three.At present,about 10 million workers in China are exposed to excessive noise,and about 1 million people suffer from hearing loss of varying degrees.As one of the most widespread and highest-risk occupational diseases,occupational hearing impairment has caused huge damage to the physical and mental health of professional workers.In addition to hearing damage,NIHL can cause headaches,dizziness,insomnia,high blood pressure,and more.At present,there is no effective method for the treatment of NIHL,but good preventive effects can be achieved by wearing protective gear and reducing noise operation time.Occupational hearing impairment is not caused solely by exposure to noise but is a combination of environmental and genetic factors.Some studies have shown that the occurrence of NIHL has a positive correlation with cumulative noise exposure,contact noise time,and noise exposure intensity.Other environmental factors such as vibration,high temperature,organic solvents,age,and high blood pressure have all been considered in previous studies to affect the development of NIHL.Numerous studies have shown that there are significant differences in the susceptibility of occupational hearing loss among different individuals.The reason for this difference is the genetic effect.Modern people have used increasingly sophisticated molecular biology techniques and have found many genetic changes related to the susceptibility of NIHL,including mitochondrial DNA(mt DNA),senile deafness gene(AHL),and plasma membrane Ca2+-ATPase 2 gene(PMCA2).The cadherin 23 gene(CDH23),KCNQ and KCNE gene family and antioxidant system related genes.The research group investigated the association between XYLT1.Object:1.To explore the relationship between the XYLT1 gene polymorphism and the haplotypes present and the susceptibility of NIHL genes in Chinese Han populations,so as to provide a strong scientific basis for better prevention of NIHL.2.To investigate the role of XYLT1 gene in combination with other factors on NIHL susceptibility.3.To search for NIHL susceptibility molecular markers suitable for Chinese Han population.Materials and Methods1.Collect 660 cases of NIHL patients who have complete physical examination data(including electrical audiometry and occupational exposure history)and use case-control study methods to match according to age,gender,type of work,and noise working age.650 cases.2.On-site questionnaire survey and individual noise exposure measurement: The survey content includes general demographic data,lifestyle habits,exposure to occupational noise,personal protection status,exposure to occupational harmful factors,and so on.According to "Workplace Physical Factor Measurement-Noise(GBZ/T189.8-2014)",Quest Sound Pro sound level meter(Quest,USA)was used to measure and record the noise intensity at each detection point in normal production conditions.3.DNA extraction and selection of SNPs: DNA from peripheral blood was extracted using the Tiangen kit(spin column method).According to the NCBI database and literature reports,34 SNPs were screened and Taqman genotyping experiments were performed on this basis.4.Statistical analysis: The questionnaire results were entered using Epidata 3.1 software,and statistical analysis was performed using SAS 9.1.3 software.Results1.The case group and control group did not show significant differences in age,sex,smoking and alcohol consumption,noise exposure level,noise-reducing working age,ear plug wearing,and family history of ear disease(P>0.05).There was a statistically significant difference in high-frequency hearing loss(P<0.001),total working age(P=0.026),ear disease(P=0.002),and family history(P=0.043).2.The distribution of all SNPs in the control group was consistent with the Hardy-Weinberg equilibrium in genetics,P > 0.05.3.Genotyping was performed on two population samples.The rs7185607 A genotype(OR=1.57,95%CI=1.07-2.31,P=0.022)and rs7205152 C gene(OR=1.63,P=0.010)were found in an additive model.Rs7191414 A genotype(OR = 1.70,P = 0.048),rs12598082 G genotype(OR = 1.76,P <0.001),and rs2311140 G(OR = 1.85,P <0.001)may be risk factors for NIHL,whereas genes rs59385104 C(OR = 0.51,P = 0.038)may reduce the susceptibility to NIHL.4.The six genotypes were analyzed in the dominant and recessive models.Only the rs2311140 G gene showed significant risk in both models(OR=2.22,P<0.001 and OR=2.08,respectively).P=0.012).In addition,the rs12598082 G gene in the dominant model also suggested that the case group had a 2-fold higher risk of NIHL than the control group(OR=2.00,P=0.003).5.By mapping the linkage disequilibrium(LD)patterns,four genotypes of the six genotypes showed strong associations,namely rs7185607,rs7205152,rs7191414,and rs12598082(D'=0.90-0.98).Based on the haplotype analysis associated with NIHL risk,the results showed that compared to other haplotypes XYLT1,the ATTA haplotypes(OR = 0.580,P = 0.001)and CCTA haplotypes(OR = 0.496,P < 0.001)The risk of developing NIHL was lower,and the CTTG haplotype(OR = 1.724,P < 0.001)increased the individual's susceptibility to NIHL.Conclusion1.Through the comparative analysis of the distribution of environmental factors in the case group and the control group,it is shown that noise exposure time and family history have significant effects on noise-induced hearing loss among numerous environmental factors.2.A correlation study between XYLT1 genotype and NIHL susceptibility found that rs7185607(AA+AC)genotype,rs7205152(CC+CT)genotype,rs7191414(AA+AT)genotype,rs12598082(GG+AG),rs2311140(GG+AG)genotype may be NIHL risk factors for onset.3.There are haplotypes in 6 sites of XYLT1 and are related to NIHL susceptibility.Haplotypes A-T-T-A and C-C-T-A may be protective factors of NIHL,and haplotype CT-T-G may increase the risk of NIHL.4.rs7185607,rs7205152,rs7191414,rs12598082,rs2311140 and haplotype CTTG of XYLT1 can be used as molecular markers of NIHL susceptibility.