| Objective Based on the establishment and follow-up of Guangxi Manganese-Exposed Workers Healthy Cohort, we used the data of field epidemiology survey, occupational health examination, Mn concentration in the air monitoring on different types of work and the GWAS by whole-genome exome BeadChip technology to explore preliminarily the early health effect and genetic polymorphism of susceptibility gene on occupational Mn exposure.Methods1. Based on a large ferromanganese refinery in Guangxi, the Guangxi Manganese-Exposed Workers Health Cohort was established in 2011, then this cohort was followed up and new research objects were recruited in 2012. In addition, the occupational epidemiological questionnaires investigation, occupational health examination and air Mn concentration monitoring in different types of work were conducted. The occupational epidemiological questionnaires investigation include demographic information, smoking history, alcohol consumption history and occupational history. Finally, the results of occupational health examination in 2011 and 2012 were described, and the effects of short-term Mn exposure on different systems were explored preliminarily.2. The whole-genome exome BeadChip experiment was conducted for 500 Mn-exposed workers using Illumina Human Exome BeadChip (V.1.0). GWAS of QTL was performed for Mn-exposed workers by bioinformatics methods with different phenotype which included urine Mn concentration (n=245) and six indicators of lung function (n=405). According to those results of different target phenotypes, the genetic polymorphism of susceptibility genes for Mn exposure was explored preliminarily.Results1. The Guangxi Manganese-Exposed Workers Healthy Cohort recruited 849 workers and followed up 87 workers which the rate of loss to follow-up is 8.4% in 2012. A total of 1888 Mn-exposed workers participated in the cohort, including 1197 male and 691 female in 2012. The average age was 40.31 years and the average seniority was 15.34 years of the cohort. The study involved different types of work which included Smelter, Human crushing worker and auxiliary worker. Craneman was involved for the first time in 2012.2. The results of Mn-exposed concentration in the workplace for different types of work showed that the types of work above the standard (0.15 mg/m3) were Human crushing worker (0.308 mg/m3), Smelter (0.204 mg/m3) and Craneman (0.197 mg/m3). The objects were divided into four groups including internal control group, low exposure group, medium exposure group and high exposure group.3. According to the gender stratification, part of occupational examination results showed that the levels of WBC in male and female were increased and Hb in male was increased, whereas PLT was decreased in 2012 comparing with 2011 (P<0.05). Comparing with 2011, the concentrations of TBIL, DBIL, IBIL in male were increased, whereas ALT in male was decreased, ALT and AST in female were decreased in 2012 (P<0.05).The levels of FVC in male and female were increased, and FEV1 in female were increased, but FEV1/FVC in male was decreased in 2012 (P<0.05). The average values of index for examination results were within normal range.4. Comparing the results of urine Mn concentration in different Mn-exposed levels, there were no statistical difference between each group (P>0.05). The urine Mn concentration was not related with Mn-CEI (P=0.059), but positively related with Mn-STEL (r=0.207, P=0.001). Moreover, the results of GWAS showed that the genetic polymorphisms of six differential genes (10 SNPs) were associated with urine Mn concentrations.5. Comparing the results of six indicators of lung function in different Mn-exposed levels, FEV1 and MVV were decreased with the increase of Mn-CEI (P<0.05). Moreover, FEV1 (r=-0.165, P=0.001) and MVV (r=-0.163, P=0.001)were negative correlation with Mn-CEI, respectively. Compared with internal control group and low exposure group, FEV1 and MVV in high exposure group were significantly decreased (P<0.05). The levels of MMEF was a negative correlation with Mn-CEI (r=-0.181, P<0.001). Compared with internal control group and low exposure group, MMEF in high exposure group and medium exposure group were significantly decreased (P<0.05). Comparing with internal control group, FEV1/FVC in low exposure group, medium exposure group and high exposure group were significantly decreased (P<0.05). But there was no correlation between the levels of FEV1/FVC with Mn-CEI (P=0.069). There were no statistical difference between four group in FVC and PEFR (P>0.05). The levels of FVC was a negative correlation with Mn-CEI (r=-0.109, P=0.029), whereas there was no correlation between the levels of PEFR and Mn-CEI (P=0.055).The results of GWAS showed that the genetic polymorphisms of 45 differential genes (61 SNPs) were associated with the levels of lung function.Conclusion1. The Guangxi manganese-exposed workers health cohort is stable, and can explore the early health effect of long-term occupational manganese exposure on multiple system basing on this cohort.2. The effects of short term occupational manganese exposure were not significant on routine blood, liver and lung function. Long-term occupational manganese exposure can cause the reduction of lung function.3. The associations of genetic polymorphisms of 6 genes (10 SNPs) and the concentrations of urine manganese were found, and these genes were related to the function of immune system through bioinformatics analysis. The relations of genetic polymorphisms of 45 genes (61 SNPs) and the levels of lung function were found, and these genes were association to the function of respiratory system by bioinformatics analysis. |
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