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Evaluation in vinyl chloride monomer-exposed workers and the relationship between liver lesions and gene polymorphisms of metabolic enzymes 被引量:6

Evaluation in vinyl chloride monomer-exposed workers and the relationship between liver lesions and gene polymorphisms of metabolic enzymes
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摘要 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. 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 (RRand 95% C1) 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.
出处 《World Journal of Gastroenterology》 SCIE CAS CSCD 2005年第37期5821-5827,共7页 世界胃肠病学杂志(英文版)
基金 Supported by the National Natural Science Foundation of China, No. 30070650 and National Key Basic Research and Development Program of China, No. 2002CB512909
关键词 氯化乙烯 肝脏损伤 基因多态性 代谢酶 Vinyl chloride monomer Hepatic lesions Cytochrome p450 2E1 Glutathione S-transferase Aldehyde dehydrogenase-2
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