| CYP2A6 genetic variation and potential consequences. | |
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MedLine Citation:
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PMID: 12406643 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Human cytochrome P450 2A6 (CYP2A6) has been shown to have large interindividual and interethnic variability in levels of expression and activity. This is thought to be largely due to genetic polymorphisms. In recent years, 13 genetic variants (CYP2A6*1-*11 and the gene duplication, *1 x 2) of CYP2A6 have been identified and a number of these have been shown to result in altered CYP2A6 enzyme activity. For example, there are alleles which result in variants that are in inactive (e.g. due to a gene deletion), have decreased activity (e.g. altered enzyme structure or transcriptional activity) or have increased activity (e.g. due to gene duplications). The resulting interindividual variation in metabolic activity may affect the metabolism of CYP2A6 substrates including nicotine, cotinine (the major metabolite of nicotine), several tobacco-specific procarcinogens, coumarin and many toxins. The frequencies of the CYP2A6 alleles vary considerably among different ethnic populations, which may partially explain the interethnic variability found in CYP2A6-related metabolic activity (e.g. nicotine metabolism), behaviors (i.e. smoking) and disease (i.e. lung cancer). Investigations of the genetic variation of CYP2A6 and its resulting effects on metabolism and health consequences are still fairly early; this review summarizes what is presently known about CYP2A6, its genetic variants and their clinical consequences. |
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Authors:
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Chun Xu; Shari Goodz; Edward M Sellers; Rachel F Tyndale |
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Publication Detail:
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Type: Journal Article; Review |
Journal Detail:
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Title: Advanced drug delivery reviews Volume: 54 ISSN: 0169-409X ISO Abbreviation: Adv. Drug Deliv. Rev. Publication Date: 2002 Nov |
Date Detail:
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Created Date: 2002-10-30 Completed Date: 2003-05-15 Revised Date: 2008-11-21 |
Medline Journal Info:
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Nlm Unique ID: 8710523 Medline TA: Adv Drug Deliv Rev Country: Netherlands |
Other Details:
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Languages: eng Pagination: 1245-56 Citation Subset: IM |
Affiliation:
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Centre for Addiction and Mental Health, University of Toronto, Toronto M5S 1A8, Canada. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Aryl Hydrocarbon Hydroxylases
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antagonists & inhibitors,
genetics* Enzyme Inhibitors / pharmacology Gene Frequency / genetics* Genetic Variation* Humans Mixed Function Oxygenases / antagonists & inhibitors, genetics* Neoplasms / enzymology, genetics Nicotine / metabolism, therapeutic use Smoking / drug therapy, genetics, metabolism |
| Chemical | |
Reg. No./Substance:
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0/Enzyme Inhibitors; 54-11-5/Nicotine; EC 1.-/Mixed Function Oxygenases; EC 1.14.14.1/Aryl Hydrocarbon Hydroxylases; EC 1.14.14.1/coumarin 7-hydroxylase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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