| Objective 1 The purpose of the present study is to investigate the associations among occupational harmful factors exposome,including high temperature,noise,dust,CO,shift,and light at night(LAN),and their interactions with metabolic syndrome(MetS)and its individual components in iron and steel workers,so as to find the priority interventionable occupational environmental factors influencing the MetS and its individual components in iron and steel workers.2 to investigate the relationship between the circadian rhythm-related genes(CLOCK,RORA and PER2)and related hormone receptor genes(MTNR1A and MTNR1B)polymorphisms as well as their haplotypes and MetS in iron and steel workers,in an attempt to provide clues for the study of the genetic epidemiology mechanism in iron and steel workers.3 to investigate the interactions between occupational harmful factors exposome and above-mentioned rhythm genes in influencing MetS in iron and steel workers,so as to provide clues for understanding the gene-environment mechanism influencing the occurrence of MetS in iron and steel workers.Methods 1 A cross-sectional study was implemented in this study to analyze the data with 7664 complete questionnaires and physical examination information which were from the cohort study on the occupational health effects in the Beijing-Tianjin-Hebei region established by our research team in February through June 2017.In this study,the available data,such as participants’ organic factors,behavioral lifestyle factors,socioeconomic and working conditions and the like,were collected through face-to-face questionnaire interviews;the exposure measurements to occupational hazard factors were collected through on-site hygienic investigation;the biochemical indicators(such as blood pressure,blood sugar,blood lipids and high-density lipoprotein cholesterol,etc.)were tested through laboratory examination;the anthropometric indicators(such as waist circumference,abdominal circumference,neck circumference,etc.)were obtained through physical examination.During the process of statistics,the harmful factors exposome was treated as the main explanatory variables.Subsequently,the restricted cubic spline(RCS)and multivariate unconditional logistic regression were used to explore the dose-response relationship and associations between the harmful factors exposome and MetS,respectively.Ultimately,using the health risk factor score(HRFS)model to explore the effects of the combined exposure to occupational risk factors on MetS.2 A case-control study was conducted in this section.In this study,according to the inclusion and exclusion criteria,621 workers with MetS and 898 workers without MetS matched with the cases’ age and gender were selected as case group and control group using SAS 9.4 programming,respectively.The polymorphisms of rs6850524 and rs1801260 loci located in CLOCK gene,rs8034880 locus located in RORA,rs934945 and rs2304672 loci located in PER2,rs2119882 locus located in MTNR1 A,as well as rs10830963 and rs1387153 located in MTNR1 B were detected using the restriction fragment length polymorphism(PCR-RFLP).Afterwards,the multivariate unconditional logistic regression was employed to analyze the association between the circadian rhythm-related genes and MetS in different genetic models.3 In this section,the research design was the same as the second section.During the process of statistics,the multiplication and additive crossover analysis as well as cumulative effects were analyzed using a log-linear model,while the high-dimensional interactions between the occupational harmful factors exposome and the circadian rhythm-related genes were estimated with the generalized multifactor dimensionality(GMDR)method.Results 1 The results of cross-sectional studies showed that: 1)the prevalence of MetS in iron and steel workerswas 37.0%,among which 37.9% for males and 26.1% for females;in the MetS components,the prevalence of abdominal obesity,elevated triglyceride level,reduced high-density lipoprotein cholesterol level,elevated blood pressure level,and elevated blood glucose level was 46.6%,32.2%,21.4%,57.9%,and 60.8%,respectively.2)The results of dose-response analysis showed that,after adjusting for potential confounding factors,a linear dose-response relationship was found between the weighted shift index(WSI)as well as high temperature cumulative exposure measurement(CEM)and MetS in iron and steel workers(overall correlation test x~2 =9.351,P=0.025 and x~2=8.611,P=0.035,respectively;nonlinear testx~2 =0.180,P=0.915 and x~2 =0.532,P=0.766,respectively);a nonlinear dose-response relationship was presented between the noise and to CO CEM and MetS in iron and steel workers(overall correlation test x~2 =21.400,P<0.001 and x~2 =10.070,P=0.018,respectively;nonlinear test c2 =0.180,P=0.915 and x~2 =8.071,P=0.017,respectively);while no correlation was found between dust CEM and MetS in iron and steel workers(overall correlation testx~2 = 2.910,P=0.406;nonlinear test x~2 =0.582,P=0.746).3)The multivariate unconditional logistic regression results between the harmful factors exposome and MetS in iron and steel workers showed that when exposed to shift,compared with the referent(WSI<551.278 days),the prevalence of MetS increased with 551.278~1475.082 days(OR=1.075,95% CI: 0.929~1.243),14750.82~2384.207 days(OR=1.088,95% CI: 0.938~1.262)and ≥2384.207 days(OR=1.204,95% CI: 1.037~1.397);when exposed to high temperature,compared with the referent(<393.270℃·years),the prevalence of MetS significantly increased with 393.270~619.876 ℃ ·years(OR=1.096,95% CI: 0.923~1.301),619.876~769.623℃·years(OR=1.286,95% CI: 1.048~1.579)and ≥769.623℃·years(OR=1.455,95% CI: 1.170~1.809);when exposed to noise,compared with the referent(<1004.68 d B(A)·years),the prevalence of MetS significantly increased with 1004.680~2048.770 d B(A)·years(OR=1.175,95% CI: 1.057~1.306)and ≥2048.77 d B(A)·years(OR=1.274,95% CI: 1.076~1.509);when exposed to CO,compared with the referent(<35.299 mg/m~3·years),the prevalence of MetS increased with 35.299 ~ 133.51 mg/m~3·years(OR=1.237,95% CI: 1.035~1.478)and ≥133.51 mg/m~3·years(OR=1.056,95% CI: 0.789~1.413);when exposed to LAN,compared to the "darkest" level,the prevalence of MetS significantly increased with the "medium"(OR=1.275,95% CI: 1.149~1.415)and "brightest"(OR=1.387,95% CI: 1.204~1.598)levels.4)The stratified analysis showed that in addition to CO CEM,other harmful factors exposome significantly increased the risk of MetS in iron and steel male workers(P<0.05);in the female workers,no statistical correlation was found between CO CEM and MetS.5)Interactions analysis results showed that LAN-WSI,age-high temperature CEM,ethnicnoise CEM and age-CO CEM multiplicative interactions were related to MetS in iron and steel workers.6)Multivariate unconditional logistic regression results between the harmful factors exposome and MetS traits in iron and steel workers showed that the noise CEM was correlated with the abdominal obesity,elevated blood glucose and reduced high density lipoprotein cholesterol(HDL-C)levels,high temperature CEM was associated with the elevated blood glucose,elevated triglyceride and blood glucose levels,WSI was associated with the elevated blood pressure level.7)HRFS models showed that in the single risk score model(SRSM),compared with the SRSM referent(0~0.604),when exposed to 0.604~0.924,0.924~1.159 and ≥1.159,the OR(95% CI)of MetS risk was 1.488(1.275~1.736),1.605(1.350~1.909)and 2.173(1.805~2.616),respectively;in the hybrid risk score model(HRSM),compared with the HRSM referent(0~0.472),when exposed to 0.472~0.708,0.708~0.902 and ≥0.902,the OR(95% CI)of the MetS risk was 1.310(1.129~1.519),1.577(1.339~1.858)and 1.991(1.668~2.377),respectively.2 Casecontrol study results from the relationship between circadian rhythm-related gene and MetS in iron and steel workers showed that after adjusting for potential confounding factors: 1)In the six genetic models,no statistical correlation was found between the CLOCK gene rs6850524 as well as rs1801260 loci and MetS in iron and steel workers.2)In the RORA gene rs8034880 locus,the risk of MetS in iron and steel workers carrying the G allele was 1.16(95% CI: 1.01~1.32)times than that of A in the allelic model;the risk of MetS in iron and steel workers carrying the GG genotype was 1.35(95% CI: 1.03~1.76)folds than that of AA in the codominant model;the risk of MetS increased by 16%(OR=1.16,95% CI: 1.01~1.33)with the increase in the number of G allele in the additive model.3)In the PER2 gene SNPs loci,in the six genetic models,no statistical correlation was found between rs934945 and MetS;in the rs2304672 locus,the risk of MetS in iron and steel workers carrying the G allele was 1.37(95% CI: 1.08~1.72)times than that of C in the allelic model;in the codominant and dominant models,the risk of MetS in iron and steel workers carrying the CG+CG or GG genotype was 1.36(95% CI: 1.04~1.78)and 1.39(95% CI: 1.07~1.80)times than that of CC,respectively;the risk of MetS in iron and steel workers carrying the CC+GG genotype was 1.34(95% CI: 1.03~1.76)times than that of CG in the overdominant model;in the additive model,with the increase in the number of G allele,the risk of MetS in iron and steel workers increased by 36%(OR=1.36,95% CI: 1.08~1.72).4)In the MTNR1 A gene rs2119882 locus,there was no statistical correlation between this locus and MetS in iron and steel workers in the six genetic models.5)In the MTNR1 B gene SNPs loci,in the codominant model of rs10830963 locus,the risk of MetS in iron and steel workers carrying CC genotype was 1.30(95% CI: 1.01~1.66)times than that of CG;the risk of MetS in iron and steel workers carrying the CG genotype was 1.26(95% CI: 1.01~1.56)times than that of CC in the overdominant model.6)There is no correlation between the haplotypes constructed by the 8 target SNPs alleles and MetS in iron and steel workers.3 Casecontrol study results from the relationship between gene-environment interactions and MetS showed that there was a multiplicative interaction between rs1387153 and CO CEM after adjusting for potential confounders(P<0.007),while none multiplication and additive interactions were observed between other gene loci and harmful risk factors exposome.2)The cumulative effects among the ROAR gene rs8034880 locus,MTNR1 B gene rs10830963 and rs1387153 loci,and PER2 gene rs2304672 locus and the harmful risk factors exposome significantly increased the risk of MetS in iron and steel workers.3)The training accuracy of the best-performing single-factor(rs1387153)and three-factor(rs6850524-rs10830963-rs1387153)interaction models identified by the GMDR method was 0.538 and 0.567,respectively,the test accuracy was 0.525 and 0.527,respectively,and their cross-consistencies were all 92.8%.The risk of MetS in iron and steel workers carrying the homozygous mutants of the corresponding genes in the best three-factor interaction model was 1.753(95% CI: 1.294~2.376)times than that in the homozygous wild type.4)The training accuracy of the best-performing five-factor(rs6850524-rs10830963-rs1387153-WSI-LAN)and six-factor gene-environment interaction models(rs6850524-rs10830963-rs1387153-high temperature CEM-WSI-LAN)identified by the GMDR method were 0.677 and 0.718,respectively.The accuracy of the test was 0.562 and 0.534 respectively,and the cross-consistency was 100.0% and 91.7%,respectively.In the best five-factor interaction model,the workers carrying the corresponding gene homozygous mutants exposed to “2384.207~” group of WSI and the "brightest" level of LAN significantly increased by 4.248(95% CI: 3.120~5.784)folds that that carrying homozygous wild type and exposed to the minimum CEM of the relevant harmful factors;moreover,in the six-factor model,it was 6.068(95% CI: 4.410~8.351)folds.Conclusions 1 WSI,light at night,high temperature,noise and CO CEM may be associated with the risk of MetS independently as well as through environmentenvironment interactions in iron and steel workers,especially in iron and steel male workers.2 The rs8034880 locus located in ROAR gene,rs10830963 and rs1387153 loci located in MTNR1 B gene,and rs2304672 locus located in PER2 gene may contribute to the risk of MetS independently in iron and steel male workers.3 The interactions among rs6850524,rs10830963,rs1387153,high temperature CEM,WSI and LAN may significantly contribute to the risk of MetS in iron and steel male workers. |
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