The Relationship Between Shift Work And Circadian Related Gene Polymorphism And Renal Function Abnormalities Among Steel Workers

Objective To investigate the effects of shift work,rhythm-related gene polymorphisms and their interactions on renal function among steel workers.Methods A total of 7031 steel workers of the HBIS GROUP TANGSTEEL COMPANY’s main production unit who participated in the 2017 annual occupational health examination,were interviewed with a standardized questionnaire and physically examine.After relevant information and blood samples were collected,we use the restricted cubic spline（RCS）model to analyze the dose-response relationship between the cumulative number of night shifts and renal function abnormalities.Then we used the results of RCS model to classify the cumulative number of night shifts were devided into four groups to analyzed the association between night shift work and renal function abnormalities with other covariate factors in a multivariate logistic regression model.Andersson additive interaction model is used to analyze the influence of the additive interaction between night shift work and other factors on renal function abnormalities.In the subsequent study,the nested case-controll study with 389 male renal function abnormalities patients and 586 male controls were randomly selected from the 7031participates with complete baseline information according to criteria of the study design.Four eligible circadian-related genes were selected,the genotype of target gene locus was determined by polymerase chain reaction（PCR）and limiting fragment length polymorphism.Finally,multi-factor logistic regression model and generalized multifactor dimensionality reduction method（GMDR）was used to analyze the influence of the interaction between genes and genes,genes and environment on renal function abnormalities.Results 1 The prevalence of renal function abnormalities in the study population,male,and female were:15.76%（1108/7031）,15.80%（1017/6436）,and 15.26%（91/595）,respectively.2 The results of RCS model analysis showed that there was non-linear dose-response relationship between the cumulative number of night shifts and renal function abnormalities（P<0.01 for overall association test,P<0.01 for nonlinear test）,after adjusting for age,gender,education level,monthly income per capita,smoking,drinking,dietary,sleep duration,insomnia,physical activity,overweight/obesity,central obesity,abnormal liver enzyme metabolism,dyslipidemia,hyperuricemia,hypertension,diabetes,high temperature,noise,dust,and carbon monoxide exposure;3 The multi-factor logistic analysis showed that the main factors affecting renal function abnormalities were night shift work,age,drinking,sleep duration,overweight/obesity,central obesity,dyslipidemia,hyperuricemia,according to the result of RCS.Compared with the cumulative number of night shifts=0 d（never shifts）,0<cumulative number of night shifts<959.88 d increased the likelihood of renal function abnormalities by 53.00%（OR=1.53,95%CI:1.22～1.92）,the cumulative number of night shifts≥2118.36 d increased the likelihood of renal function abnormalities by 58.00%（OR=1.58,95%CI:1.26～2.97）;4 Compared with duration of night shifts≤20 years and average frequency of night shifts≤7 nights/month,those with a duration of night shifts≤20 years and average frequency of night shifts>7nights/month or a duration of night shifts>20 years and average frequency of night shifts>7 nights/month showed significantly elevated odds of renal function abnormalities（OR=1.63,95%CI:1.23～2.14;OR=1.31,95%CI:1.07～1.60）;5 There is an interaction between hyperuricemia,abnormal liver enzyme metabolism,dust exposure and the cumulative number of night shifts based on multiplicative model(P_interaction<0.05).The interaction between physical activity,overweight/obesity,central obesity and average frequency of night shifts based on multiplicative model(P_interaction<0.05).There is an additive model-based interaction between average frequency of night shifts and overweight/obesity,central obesity,and hyperuricemia（RERI and AP confidence interval don’t include 0）;6 The PER2 gene rs2304672 polymorphism was associated with renal function abnormalities significantly,including the codominant model（CG vs CC）（OR=1.54,95%CI:1.09～2.17）,the dominant model（CG,GG vs CC）（OR=1.44,95%CI:1.03～2.02）,and the overdominant model（CG vs CC）（OR=1.56,95%CI:1.11～2.19）;7There is no interaction between PER2（rs2304672）gene and MTRN1B gene（rs1387153）,CLOCK gene（rs1801260）and RORA gene（rs8034880）based on multiplicative model and additive model;8 CLOCK gene rs1801260 locus polymorphism has a combined effect with night shift work,compared with day workers with TT genotype,short-term shift workers（0<cumulative number of night shifts<959.88 d）with TC genotype have an increased risk of renal function abnormalities（OR=2.48,95%CI:1.15～5.35）;PER2 gene rs2304672 locus polymorphism has a combined effect with night shift work,compared with day workers with CC or GG genotype,shift workers（959.88≤cumulative number of night shifts<2118.36 d or cumulative number of night shifts≥2118.36 d）with CG genotype have an increased risk of renal function abnormalities（OR=2.17,95%CI:1.10～4.26;OR=2.16,95%CI:1.13～4.16）;RORA gene rs8034880 locus polymorphism has a combined effect with night shift work,compared with day workers with AA genotype,short-term shift workers（0<cumulative number of night shifts<959.88 d）with AG genotype have an increased risk of renal function abnormalities（OR=1.99,95%CI:1.06～3.74）,but no interaction was found based on the multiplication model.Conclusions 1 There is a nonlinear dose response relationship between the cumulative number of night shifts and renal function abnormalities;2 Night shift work,age,drinking,sleep duration,overweight/obesity,central obesity,dyslipidemia,and hyperuricemia are the main independent risk factors for renal function abnormalities;3 There is an interaction between shift work and physical activity level,overweight/obesity,central obesity,hyperuricemia,abnormal liver enzyme metabolism,and dust exposure based on a multiplicative or additive model;4 PER2 gene rs2304672 locus gene polymorphism is associated with male steel worker renal function abnormalities;5 The PER2 gene rs2304672 locus,the CLOCK gene rs1801260 locus,and the RORA gene rs8034880 locus gene polymorphism have a joint effect with shifting,but there is no interaction based on the multiplicative model.Figure 6;Table 32;Reference 138...