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Citation
Tags
HERO ID
196814
Reference Type
Journal Article
Subtype
Review
Title
Genetic polymorphism in CYP2E1: Population distribution of CYP2E1 activity
Author(s)
Neafsey, P; Ginsberg, G; Hattis, D; Johns, DO; Guyton, KZ; Sonawane, B
Year
2009
Is Peer Reviewed?
1
Journal
Journal of Toxicology and Environmental Health, Part B: Critical Reviews
ISSN:
1093-7404
EISSN:
1521-6950
Volume
12
Issue
5
Page Numbers
362-388
Language
English
PMID
20183527
DOI
10.1080/10937400903158359
Web of Science Id
WOS:000271375100003
URL
http://dx.doi.org/10.1080/10937400903158359
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Abstract
Cytochrome P-450 2E1 (CYP2E1) is a key enzyme in the metabolic activation of a variety of toxicants including nitrosamines, benzene, vinyl chloride, and halogenated solvents such as trichloroethylene. CYP2E1 is also one of the enzymes that metabolizes ethanol to acetaldehyde, and is induced by recent ethanol ingestion. There is evidence that interindividual variability in the expression and functional activity of this cytochrome (CYP) may be considerable. Genetic polymorphisms in CYP2E1 were identified and linked to altered susceptibility to hepatic cirrhosis induced by ethanol and esophageal and other cancers in some epidemiological studies. Therefore, it is important to evaluate how such polymorphisms affect CYP2E1 function and whether it is possible to construct a population distribution of CYP2E1 activity based upon the known effects of these polymorphisms and their frequency in the population. This analysis is part of the genetic polymorphism database project described in the lead article in this series and followed the approach described in that article (Ginsberg et al., 2009, this issue). Review of the literature found that there are a variety of CYP2E1 variant alleles but the functional significance of these variants is still unclear. Some, but not all, studies suggest that several upstream 5' flanking mutations affect gene expression and response to inducers such as ethanol or obesity. None of the coding-region variants consistently affects enzyme function. Part of the reason for conflicting evidence regarding genotype effect on phenotype may be due to the wide variety of exposures such as ethanol or dietary factors and physiological factors including body weight or diabetes that modulate CYP2E1 expression. In conclusion, evidence is too limited to support the development of a population distribution of CYP2E1 enzyme activity based upon genotypes. Health risk assessments may best rely upon data reporting interindividual variability in CYP2E1 function for input into physiologically based pharmacokinetic (PBPK) models involving CYP2E1 substrates.
Keywords
Pharmacy And Pharmacology; Polymorphism; Population genetics; Enzymes; Genotype & phenotype; Metabolism
Tags
•
Chloroprene
Cited 2010 Final
•
Tetrachloroethylene (Perc) (Final, 2012)
Hazard
Susceptibility
OPPT REs
•
OPPT_1-Bromopropane (1-BP)_A. Summary
Cited in TSCA RE related document
•
OPPT_1-Bromopropane (1-BP)_F. Human Health
Total – title/abstract screening
On topic
Supplemental search
•
OPPT_Perchloroethylene (Perc)_C. Engineering
Total – title/abstract screening
Off topic
•
OPPT_Perchloroethylene (Perc)_D. Exposure
Total – title/abstract screening
Off topic
•
OPPT_Perchloroethylene (Perc)_E. Fate
Total – title/abstract screening
Off topic
•
OPPT_Perchloroethylene (Perc)_F. Human Health
Total – title/abstract screening
Off topic
•
OPPT_Trichloroethylene (TCE)_C. Engineering
Total – title/abstract screening
Off topic
•
OPPT_Trichloroethylene (TCE)_D. Exposure
Total – title/abstract screening
Off topic
•
OPPT_Trichloroethylene (TCE)_E. Fate
Total – title/abstract screening
Off topic
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