title: The GST T1 and CYP2E1 genotypes are possible factors causing vinyl chloride induced abnormal liver function.
abstract: Vinyl chloride monomer (VCM) is hepatotoxic as well as carcinogenic in humans. There are reports that exposure to VCM seems to induce abnormal liver function, liver fibrosis, cirrhosis, portal hypertension, and angiosarcoma of the liver. In vivo, VCM is metabolized by cytochrome P450 2E1 (CYP2E1) to form the electrophilic metabolites, chloroethylene oxide (CEO) and chloroacetaldehyde (CAA), which may either cause cell damage or be further metabolized and detoxified by glutathione S-transferases (GSTs). This study investigated whether or not the genotypes CYP2E1, glutathione S-transferase theta (GST T1) and mu (GST M1) correlated with abnormal liver function found in vinyl chloride exposed workers. For this study, 251 workers from five polyvinyl chloride plants were enrolled. The workers were classified into two exposure groups (high and low) and the degree of exposure was determined based on their job titles and airborne VCM concentration. The activity of serum alanine aminotransferase (ALT) was used as the parameter of liver function. The genotypes CYP2E1, GST T1 and GST M1 were determined by polymerase chain reaction and restriction fragment length polymorphism on peripheral white blood cell DNA. Other potential risk factors were also ascertained and the confounding effect was adjusted accordingly. Stratified analyses were used to explore the correlation between the alteration of liver function and the genotypes CYP2E1, GST T1 and GST M1 among the workers exposed to different levels of VCM. The following results were obtained (1) at low VCM exposure, the odds ratio (OR) of positive GST T1 on abnormal ALT was 3.8 (95% CI 1.2-14.5) but the CYP2E1 genotype was not associated with abnormal ALT. (2) At high VCM exposure, a c2c2 CYP2E1 genotype was associated with increased OR on abnormal ALT (OR 5.4, 95% CI 0.7-35.1) and positive GST T1 was significantly associated with decreased OR on abnormal ALT (OR 0.3, 95% CI 0.1-0.9). (3) Multiple linear and logistic regression also showed strong interactions of the VCM exposure to CYP2E1 as well as to the GST T1 genotype. These observations suggest that the two genotypes, CYP2E1 and GST T1, may play important roles in the biotransformation of VCM, the effect of which leads to liver damage.
authors.affiliation: Institute of Occupational Medicine and Industrial Hygiene, College of Public Health, National Taiwan University, Taipei.
authors.forename: C Y
authors.initials: CY
authors.lastname: Huang
authors.forename: K L
authors.initials: KL
authors.lastname: Huang
authors.forename: T J
authors.initials: TJ
authors.lastname: Cheng
authors.forename: J D
authors.initials: JD
authors.lastname: Wang
authors.forename: L L
authors.initials: LL
authors.lastname: Hsieh
mesh_terms: D000328:Adult; D000410:Alanine Transaminase / Q000378:metabolism; D015992:Body Mass Index; D002273:Carcinogens / Q000633:toxicity*; D056486:Chemical and Drug Induced Liver Injury / Q000235:genetics* / Q000378:metabolism*; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics*; D005260:Female; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D007527:Isoenzymes / Q000235:genetics*; D008111:Liver Function Tests; D008297:Male; D016273:Occupational Exposure / Q000009:adverse effects*; D012044:Regression Analysis; D014752:Vinyl Chloride / Q000633:toxicity*
chemical_list: D002273:Carcinogens; D007527:Isoenzymes; D019392:Cytochrome P-450 CYP2E1; D005982:Glutathione Transferase; D000410:Alanine Transaminase; D014752:Vinyl Chloride