Polymorphisms of microsomal epoxide hydrolase in French vinyl chloride workers.
OBJECTIVE
The purpose of this study was to determine if polymorphisms in microsomal epoxide hydrolase, an enzyme involved in the metabolism of reactive intermediates of vinyl chloride (VC), contribute to the variable susceptibility to the mutagenic effects of vinyl chloride among exposed workers.


METHODS
Polymorphisms at codons 113 and 139 were determined in DNA samples from 211 French vinyl chloride workers. Genotypes were stratified into low, medium and high activity groups and odds ratios and 95% confidence intervals were determined for the presence of one or both of two VC-induced mutant biomarkers (mutant ras-p21 and mutant p53) by logistic regression adjusting for age, smoking, drinking and cumulative VC exposure.


RESULTS
Compared to the low-activity microsomal epoxide hydrolase genotype stratum, the odds ratio for the presence of the VC-induced mutant biomarkers increased to 1.16 (95% CI: 0.64-2.10) in the medium-activity genotype stratum and to 1.35 (95% CI: 0.66-2.77) in the high-activity genotype stratum. The test for trend was not statistically significant and was in the opposite direction from that expected based on increasing removal of reactive intermediates with increasing activity.


CONCLUSIONS
The results suggest that polymorphisms in microsomal epoxide hydrolase do not play a significant role in susceptibility to the mutagenic effects of vinyl chloride.
Li
Yongliang
Y
Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, NY 10032, USA.
Lee
Stephen
S
Marion
Marie-Jeanne
MJ
Brandt-Rauf
Paul W
PW
D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D002273:Carcinogens / Q000378:metabolism* / Q000633:toxicity; D015331:Cohort Studies; D004851:Epoxide Hydrolases / Q000187:drug effects / Q000235:genetics*; D005602:France; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016296:Mutagenesis / Q000187:drug effects / Q000235:genetics; D016273:Occupational Exposure / Q000009:adverse effects / Q000032:analysis*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000187:drug effects; D014752:Vinyl Chloride / Q000378:metabolism* / Q000633:toxicity
D015415:Biomarkers; D002273:Carcinogens; D004851:Epoxide Hydrolases; D014752:Vinyl Chloride