Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:The GST T1 and CYP2E1 genotypes are possible factors causing vinyl chloride induced abnormal liver function. 924 25

This study was designed to determine whether vinyl chloride monomer (VCM) exposure is associated with liver fibrosis. A total of 347 workers with occupational exposure to VCM were systemically examined using liver ultrasonography and routine liver function tests. Vinyl chloride monomer cumulative dose (ppm-month) was estimated by summing the products of air VCM concentration levels and months of employment. Liver fibrosis was defined in subjects with precirrhosis and cirrhosis of liver diagnosed using ultrasonography. Significantly increased risks of developing liver fibrosis were found in workers who had history of high exposure jobs (odds ratio 5.5, 95% confidence interval 1.7-25.4) when compared with workers who did not have history of high exposure jobs. We concluded that there was an increased risk of developing liver fibrosis in PVC workers who had high exposure to VCM.
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PMID:Liver fibrosis in asymptomatic polyvinyl chloride workers. 1535 62