Evaluation in vinyl chloride monomer-exposed workers and the relationship between liver lesions and gene polymorphisms of metabolic enzymes

Abstract

Aim: To analyze occupational health hazards exposure to doses lower than the Chinese occupational health standard in a selected VC polymerization plant in China, and also to elucidate the relationship between genetic polymorphisms and genetic susceptibility on liver lesions of workers exposed to vinyl chloride monomer(VCM).

Methods: In order to explore the mechanism of VCM-related health effects, we used a case-control design to investigate the association between the genetic polymorphisms of metabolic enzymes and liver lesions in workers occupationally exposed to VCM. Genotypes of CYP2E1, GSTT1, GSTM1, ALDH2 and ADH2 were identified using PCR and PCR-RFLP.

Results: Even when the concentration of VCM was lower than the current Chinese occupational health standard, neurasthenia, pharyngeal irritation, liver ultrasonography abnormalities and hemoglobin disorders were significantly higher in exposure subjects compared to non-exposure subjects, and the relative risks (RR and 95% CI) were 1.74 (1.06-2.85), 1.97 (1.56-2.48), 10.69 (4.38-26.12), and 2.07 (1.20-3.57). CYP2E1 c1c2/c2c2 genotype was significantly associated with liver damages (OR 3.29, 95% CI 1.51-7.20, P<0.01).

Conclusion: The incidences of neurasthenia and liver ultrasonography abnormalities significantly increase when the cumulative exposure dose increases. The genotypes of metabolic enzymes (CYP2E1 c1c2/c2c2, null GSTT1 and ADH2 1-1) play important roles in VCM metabolism. Polymorphisms of CYP 2E1, GSTT1 and ADH2 may be a major reason of genetic susceptibility in VCM-induced hepatic damage.

Figure 1

PCR products A: PCR products of GSTT1 and GSTM1. M: DNA marker; lanes 1-5 DNA products; lane 1: none; lane 2: GSTT1 and GSTM1; lane 4: GSTM1; lanes 3, 5: GSTT1. B: PCR-RLFP products of CYP2E1. M: DNA marker; lanes 1-5 DNA products. Homozygous c1c1 shows a single band with 410 bp; homozygous c2c2 shows two bands with 290 bp and 120 bp; and heterozygous c1c2 shows all three bands. C: PCR products of ALDH2. Lanes 1-6 DNA products; M: DNA marker. Homozygous 2-2 shows a single band with 135 bp; homozygous 1-1 shows two bands with 125 bp and 10 bp; and heterozygous 1-2 shows all the three bands. D: PCR products of ADH2. Lanes 1-6: DNA products; M: DNA marker. Homozygous 1-1 shows a single band with 95 bp; homozygous 2-2 shows two bands with 60 bp and 35 bp; and heterozygous 1-2 shows all the three bands.