Effect of the CYP2E1 genotype on vinyl chloride monomer-induced liver fibrosis among polyvinyl chloride workers
Journal
Toxicology
Journal Volume
239
Journal Issue
44198
Pages
34-44
Date Issued
2007
Author(s)
Abstract
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. ? 2007 Elsevier Ireland Ltd. All rights reserved.
SDGs
Other Subjects
aldehyde dehydrogenase isoenzyme 2; cytochrome P450 2E1; glutathione transferase T1; polyvinylchloride; adult; article; calculation; comparative study; concentration response; controlled study; disease predisposition; echography; genetic polymorphism; genotype; human; liver fibrosis; liver injury; male; metabolism; polymerase chain reaction; priority journal; restriction fragment length polymorphism; risk assessment; Adult; Air Pollutants, Occupational; Aldehyde Dehydrogenase; Carcinogens; Cytochrome P-450 CYP2E1; Dose-Response Relationship, Drug; Genetic Predisposition to Disease; Genotype; Glutathione Transferase; Humans; Liver Cirrhosis; Occupational Exposure; Polymorphism, Genetic; Polymorphism, Restriction Fragment Length; Risk Assessment; Taiwan; Vinyl Chloride
Type
journal article