EFFECT OF THE CYP2E1 GENOTYPE ON VINYL CHLORIDE MONOMER-INDUCED LIVER FIBROSIS AMONG POLYVINYL CHLORIDE WORKERS
Resource
TOXICOLOGY v.239 n.1-2 pp.34-44
Journal
TOXICOLOGY
Journal Volume
v.239
Journal Issue
n.1-2
Pages
34-44
Date Issued
2007
Date
2007
Author(s)
HSIEH, HUI-I
CHEN, PAU-CHUNG
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. (c) 2007 Elsevier Ireland Ltd. All rights
reserved.
Subjects
occupational exposure
vinyl chloride monomer
liver fibrosis
metabolizing genetic polymorphisms
Type
journal article
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