Effect of the CYP2E1 genotype on vinyl chloride monomer-induced liver fibrosis among polyvinyl chloride workers.
Although a relationship between vinyl chloride monomer (VCM) and liver cirrhosis has been reported, the underlying mechanisms are not clear. Cytochrome P450 2E1 (CYP2E1), aldehyde dehydrogenase 2 (ALDH2) and glutathione S-transferase theta 1 (GSTT1) enzymes are involved in activation and detoxification of VCM, and thus may be important determinants of interindividual susceptibility to VCM-induced liver damage, including liver cirrhosis. The objective of this study was to evaluate if metabolizing genetic polymorphisms could modify individual susceptibility to liver fibrosis of the VCM exposure. CYP2E1, ALDH2, and GSTT1 polymorphisms were determined by the PCR-RFLP method among 320 workers who were employed in five polyvinyl chloride manufacturing plants. Cumulative VCM exposure levels for study subjects were calculated using a job exposure matrix model. Thirteen workers were diagnosed as having liver fibrosis by using ultrasonography. We observed a dose-response trend between VCM exposure and liver fibrosis. Regarding the results on genetic polymorphisms, CYP2E1 c2c2 genotype showed a significant increase in the risk of liver fibrosis as compared to those with CYP2E1 c1c1 or c1c2 genotypes. No differences were observed between GSTT1 and ALDH2 genotypes and liver fibrosis. In summary, our result suggests that genetic polymorphism in CYP2E1 may be responsible for individual differences in susceptibility to liver fibrosis with regard to chronic VCM exposure. Thus, polymorphism analysis of metabolizing enzymes might be useful in the risk assessment of liver damage in workers with VCM exposure.
Institute of Occupational Medicine and Industrial Hygiene, College of Public Health, National Taiwan University, Zhongzheng District, Taipei City, Taiwan.
Hui-I
HI
Hsieh
Pau-Chung
PC
Chen
Ruey-Hong
RH
Wong
Jung-Der
JD
Wang
Pei-Ming
PM
Yang
Tsun-Jen
TJ
Cheng
D000328:Adult; D000395:Air Pollutants, Occupational / Q000633:toxicity*; D000444:Aldehyde Dehydrogenase / Q000235:genetics / Q000378:metabolism; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D002273:Carcinogens / Q000633:toxicity*; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000000981:diagnostic imaging / Q000201:enzymology / Q000235:genetics*; D016273:Occupational Exposure / Q000009:adverse effects; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D018570:Risk Assessment; D013624:Taiwan; D014463:Ultrasonography; D014752:Vinyl Chloride / Q000633:toxicity*
D000395:Air Pollutants, Occupational; D002273:Carcinogens; D019392:Cytochrome P-450 CYP2E1; C096127:ALDH2 protein, human; D000444:Aldehyde Dehydrogenase; D000071396:Aldehyde Dehydrogenase, Mitochondrial; C413545:glutathione S-transferase T1; D005982:Glutathione Transferase; D014752:Vinyl Chloride