The Internal Exposure Marker In Plasma Of Manganese Workers And Study Of Genome-Wide Exons Polymorphisms

Objective Based on the established Guangxi Manganese-Exposed Workers Healthy Cohort, the plasma manganese levels of workers were detected by inductively coupled plasma mass spectrometry (ICP-MS) and graphite furnace atomic absorption spectrometry, and the internal exposure markers in blood and genetic polymorphism of susceptibility gene on Mn-exposed workers were explored preliminarily the through Exome Bead Chip technology and Genome-Wide Association Study.Methods1. Based on a large ferromanganese refinery in Guangxi, the demographic information, smoking history, alcohol consumption history and occupational history of Mn-exposed workers who participated occupational health examinations in 2012 were collected using occupational epidemiological questionnaires and occupational health examination. Simultaneously, the air Mn levels of different working types were monitored and the levels of blood Mn, plasma Mn and other trace elements in Mn-exposed workers were detected by ICP-MS and GFFAS. Additionally, the internal exposure markers in blood of Mn-exposed workers were explored preliminarily through evaluating the dose-effect relationship between the levels of Mn dust and the levels of blood Mn, plasma Mn and other trace elements.2. The Exome Bead Chip experiment was conducted for 376 Mn-exposed workers. The GWAS of QTL for Mn-exposed workers was performed by bioinformatics methods with different phenotypes which included blood Mn and plasma Mn levels. According to those results, the genetic polymorphism of susceptibility genes in manganese metabolism was explored preliminarily.Result1. The air Mn concentration in the workplace for different types of work were detected and the study population were divided into two groups based on the national standard (0.15 mg/m3) which including the control group (Mn-TWA<0.15 mg/m3) and the exposed group (Mn-TWA≥0.15 mg/m3).2. Comparing the plasma Mn concentration in two groups, the results showed that the plasma Mn levels in the exposed group (n=25) and the control group (n=15) were 3.16 ug/L and 3.22 ug/L, respectively, which had no significant difference (P>0.05). In addition, the partial correlation analysis was performed between the levels of plasma Mn and other metal elements, and there was a positive correlation between plasma Mn and Ni (r=0.544, P<0.01), while significant negative association was observed between plasma Mn and Cd(r=-0.425,P<0.05).3. The blood Mn levels were significantly higher in the exposed group (17.73 ug/L) comparing the control group (12.00 ug/L) (P<0.05). The plasma Mn levels in two groups were 3.01 ug/L and 3.13 ug/Lrespectively, and there were no significant difference (P>0.05). Moreover, there were a positive correlation between the levels of blood Mn and plasma Mn (r=0.323, P<0.01).4. The levels of blood Mn had a positive correlation to Mn-TWA (r=0.159, P=0.015), Mn-STEL (r=0.323, P<0.000) respectively. The results of GWAS showed that the genetic polymorphisms of TTN (rs248772, rs249011, rs249060, rs249099, and rs249127), PDE4D (rs2265944), and APOBEC3H (rs2273063 and rs 1609556) were associated with the blood Mn levels, and the genetic polymorphisms of MTRR(rs443883), TRIM5(rs883558 and rs883596), NOX5(rs1172903) were associated with the plasma Mn levels. These genetic variations may cause the difference of blood Mn levels or plasma Mn levels among different individuals by altering the structure and function of ion transporter proteins.Conclusion1. Blood Mn had a correlation to air Mn concentration, and it can be used as an internal Mn-exposured biomarker. However, plasma Mn had no correlation to air Mn concentration, and it was not suitable as an internal Mn-exposured biomarker ultimately. There was a great difference between blood Mn and plasma Mn levels among different individuals.2. The relations of genetic polymorphisms of TTN, PDE4D, APOBEC3H (8 SNPs) and the blood Mn levels were identified, and the associations of genetic polymorphisms of MTRR, TRIM5, and NOX5 (4 SNPs) and the plasma Mn levels were found. The bioinformatics analysis showed that these genes were related to the function of ion transporters, and these SNPs will be verified in the further research.