Influence Of Environment-gene Interactions On Sleep Quality Of Different Occupations In Xinjiang

Objective: To investigate the occupational stress and sleep quality of different occupations in Xinjiang,and analyze its relationship.To research the effect of neurotransmitters for occupational stress and sleep quality in this crowd.The effect of gene polymorphism of DRD2,NET,COMT,GABRA,5-HTR2 A and 5-HTTLPR on sleep quality was also investigated.Through comparison of the differences of DNA methylation in the promoter region of 5-HTT gene between sleep quality problem groups or occupational stress groups to explore the effect of epigenetics in the relationship between occupational stress and sleep quality.Analysis gene-gene and gene-environment(occupational stress)interaction on sleep quality in different occupations in Xinjiang.Our study provided epidemiological information on occupational stress and sleep quality of different occupations in Xinjiang,thus providing scientific basis for improving sleep quality.Methods: 1)This study adopts multistage sampling.Using Occupational Stress Inventory Revised Edition(OSI-R),Effort-reward imblance(ERI)and Pittsburgh sleep quality index(PSQI)to survey a total of 2650 workers.2)240 subjects were extracted randomly to test plasma 5-HT,NE,E,DA,GABA.Structural equation modeling was used to analyze the relationship between occupational stress,neurotransmitters and sleep quality.3)700 different occupations workers were selected randomly,using SNaPshot method to detect 10 gene polymorphisms of DRD2(rs1799732,rs1800497),NET(rs2242446,rs5569),GABRA(rs3219151,rs2279020),COMT(rs4680),5-HTR2A(rs6311,rs6313)and 5-HTTLPR.Furthermore,find the susceptible genes of sleep quality by comparing the genotype distributions between different sleep quality groups.4)Using Methyl Target technique to detect the degree of DNA methylation in the 5-Hydroxytamine transporter(5-HTT)promoter region.5)Combining with SHEsis haplotype analysis,Generalized Multifactor Dimensionality Reduction to construct the best models of gene-gene,gene-environment interaction effects,the odds ratio(OR)and 95%confidenceinterval(CI)of the risk of sleep quality were calculated by multivariate logistic regression analysis.Results: 1)A total of 2650 questionnaires were provided,and 2400 validated ones were collected.The validation rate was 90.6%.2)In this investigation,the scores of occupational stress among primary and secondary school teachers,the petroleum workers and the railway workers were higher than university teachers,administrative staff and bank staff(P<0.05).The score of occupational role of working age 10~20 years were higher than >20 years workers(P<0.05).The scores of occupational role and personal strain of male was higher than the female(P<0.05).The scores of occupational role and personal strain of Ethnic minorities was higher than Han nationality(P<0.05).The score of occupational role of master's degree were higher than the undergraduate and the technical secondary school education(P < 0.05).The scores of occupational role and personal strain of smokers was higher than non-smokers(P < 0.05).The score of occupational role of drinkers were higher than the non-drinkers(P<0.05).3)The score of external cost,internal input and work reward were different among different occupations(P < 0.05),in which petroleum workers,primary and secondary school teachers and railway workers were effort-reward imbalance.The score of external cost,internal input and work reward were different among working age(P<0.05).The score of internal input and work reward were different among gender(P < 0.05),in which male was effort-reward imbalance.The score of external cost,internal input and work reward were different among education level(P<0.05),in which master's degree was effort-reward imbalance.The score of internal input and work reward were different among smoking status(P<0.05),in which smokers was effort-reward imbalance.4)The PSQI score value was(4.92±3.15)points.PSQI total score > 5 as a standard,36.4% of the different occupation workers had poor sleep quality.The scores of sleep quality among university teachers,the petroleum workers and the railway workers were higher than primary and secondary school teachers,administrative staff and bank staff(P < 0.05).The score of sleep quality of working age >20years and 10 ~ 20 years were higher than ?10 years workers(P < 0.05).With the increase of working years,the score of sleep quality decreased.Female sleep quality score higher than male(P<0.05).Divorced or widowed workers sleep quality scores were higher than the unmarried workers(P<0.05).Smokers sleep quality score higher than non-smokers(P < 0.05).5)There were significant differences in PSQI scores,subjective sleep quality,sleep duration,sleep disorders,sleep medication and daytime dysfunction of different job strain groups(P<0.05),in which sleep duration,sleep disorders,hypnotic drugs and daytime dysfunction of high job straingroup were higher than low job strain group(P<0.05).With the increasing of job strain,the sleep quality of the subjects get worse.There were significant differences in PSQI scores,sleep latency,sleep duration,sleep disorders,hypnotic drugs and daytime dysfunction of different effort-reward imbalance groups(P < 0.05),in which high effort-low reward group were higher than low effort-high reward group.6)The level of5-HT and NE of high job strain group were higher than medium and low job strain group(P < 0.05).The level of NE of high effort-low reward group were higher than low effort-high reward group(P<0.05).The levels of 5-HT,DA and E in poor sleep quality group were higher than those in good sleep quality group(P < 0.05).Multivariate correlation analysis showed that the occupational role and personal strain correlated positively with the 5-HT,NE(P<0.05)and personal resources correlated inversely with DA in different occupations workers(P<0.05).External cost was positively correlated with NE(P<0.05),and internal input correlated inversely with 5-HT(P<0.05).There was negative correlation with GABA of personal stress and external cost(P<0.05).The levels of 5-HT,NE,DA and E were positively correlated with sleep quality(P<0.05),and GABA was negatively correlated with sleep duration(P<0.05).7)Multivariate Logistic regression analysis found that the factors affecting sleep quality were: job type,personal stress,external cost,work reward,internal input,5-HT,NE and DA.Based on the structural equation model of occupation stress-physiological stress response(neurotransmitter)-sleep quality found that occupational stress,ERI and physiological stress response has a direct impact on sleep quality,and occupational stress has a direct effect on the physiological stress response,and physiological stress response was the mediating factor of occupational stress on sleep quality.8)Dopamine D2 receptor gene(DRD2),norepinephrine transporter(NET)gene,?-aminobutyric acid type A receptor(GABRA)gene,catechol-O-methyltransferase(COMT)gene,serotonin 2A receptor(5-HTR2A)gene and 5-HTTLPR gene of 10 tagSNPs loci genotype and allele frequency were fited Hardy-Weinberg equilibrium,for each individual P>0.05,indicates that the gene frequency has reached a population representation of genetic equilibrium.9.Genetic susceptibility analysis of sleep quality: ?DRD2 gene: The A1A1 genotype of rs1800497 was associated with long sleep latency and sleep duration and more sleep disorder and sleep medication;A1A1 genotype had a higher risk of poor sleep quality(OR=1.938,95%CI: 1.228-3.058).? NET gene: The AA genotype of rs5569 was associated with high subjective sleep quality and sleep efficiency;AG genotype(OR=1.569,95%CI:1.109-2.220)and AA genotype(OR=1.569,95%CI: 1.109-2.220)had higher risk of poorsleep quality.? GABRA1 gene: The G allele frequency of rs2279020 mutation was64.9%.The GG genotype of rs2279020 was associated with high subjective sleep quality and sleep efficiency;GG genotype had a higher risk of poor sleep quality(OR=1.183,95%CI: 1.064-2.015).? 5-HTR2 A gene: The GG genotype of rs6311 was associated with high subjective sleep quality and more daytime dysfunction;GG genotype had a higher risk of poor sleep quality(OR=1.929,95%CI: 1.222-3.047).The CC genotype of rs6313 was associated with high subjective sleep quality and sleep efficiency;GG genotype had a higher risk of poor sleep quality(OR=3,344,95%CI: 2.062-5.422).? 5-HTTLPR gene:The SS genotype of 5-HTTLPR was associated with high subjective sleep quality;SS genotype had a higher risk of poor sleep quality(OR=2.118,95%CI: 1.053-4.257).?COMT gene: There was no difference in sleep quality between genotype group of rs4680(P > 0.05).10)The methylation level of CpG2,CpG4,CpG6,CpG8,CpG12,CpG13,CpG16,CpG17,CpG47 and CpG58 of 5-HTT in high occupational stress group were lower than low occupational stress group(P < 0.05).The methylation level of CpG5,CpG8,CpG13,CpG14,CpG16,CpG30,CpG34 and CpG47 of 5-HTT in poor sleep quality group were lower than good sleep quality group(P < 0.05).Among poor sleep quality workers,the methylation level of CpG13,CpG16,CpG34 and CpG47 of 5-HTT in high occupational stress group were lower than low occupation stress group(P<0.05).11)Analysis the relationship between the haplotype and sleep quality found that haplotype of I-A1 of DRD2 gene was risk for sleep quality,and I-A2 was the protective haplotype;haplotype of T-A of NET gene was risk for sleep quality,and T-G was the protective haplotype;haplotype of G-C of 5-HTR2 A gene was risk for sleep quality,and G-T was the protective haplotype;haplotype of G-C of GABRA gene was risk for sleep quality,and A-C was the protective haplotype.12)GMDR software analysis found the interaction model of rs1800497,rs2279020 and rs6313 was the best gene-gene model.Logistic regression analysis showed that the interaction of DRD2 rs1800497,GRBRA1 rs2279020 and 5-HTR2 A rs6313 were the risk factors on sleep quality of Xinjiang different occupations crowd(OR=1.186,95%CI: 1.015-3.432).The interaction model of rs6313,occupational stress and ERI was the best gene-environmet model.Logistic regression analysis showed that the interaction of rs6313,occupational stress and ERI were increased the risk of poor sleep quality(OR=1.171,95%CI: 1.012-1.355).Conclusions: 1)The level of occupational stress was higher in male,ethnic minorities,10-20 years working age,married,smoking and drinking of the primary and secondary school teachers,petroleum workers,and railway workers.Male,highly educated petroleum workers,primary andsecondary school teachers and railway workers had effort-reward imbalance.2)The prevalence of poor sleep quality and PSQI score in Xinjiang different occupations crowd were higher,which indicates that sleep quality was poor.3)With the increasing of occupational stress and effort-reward imbalance,the sleep quality get worse.4)Neurotransmitters should affect occupational stress and sleep quality of this group;Work type(railway staff,field workers),personal strain,external cost,internal input,5-HT,NE and DA were the risk factors of sleep quality,and the work reward was the protective factor of sleep quality;Occupational stress,ERI and physiological stress response has a direct impact on sleep quality,and occupational stress has a direct effect on the physiological stress response,and physiological stress response was the mediating factor of occupational stress on sleep quality.5.DRD2 gene rs1800497 locus A1A1 genotype,NET gene rs5569 locus AA genotype,GABRA1 gene rs2279020 locus GG genotype,5-HTR2 A gene rs6311 locus GG genotype and r6313 locusCC genotype and 5-HTTLPR gene SS genotype were susceptible genotypes of sleep quality problems.6)The decrease of 5-HTT gene promoter methylation may increase the risk of occupational stress and sleep quality,and the methylation level of 5-HTT gene may play a role in the regulation of occupational stress and sleep quality.7)The tag SNPs of DRD2 gene,NET gene,GABRA gene and 5-HTR2 A gene could affect sleep quality sleep quality by haplotype.8)The interaction effects of DRD2 rs1800497,GRBRA1 rs2279020 and 5-HTR2 A rs6313 locus could increase the risk of poor sleep quality of Xinjiang different occupations workers;meanwhile the interactive effects of rs6313,occupational stress and ERI may increase the risk of suffering from poor sleep quality of Xinjiang different occupations workers.