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The CYP2A6 enzyme inactivates 90% of nicotine in humans. Large variation in nicotine metabolism rates among those with CYP2A6*1xN duplication suggested multiple gene copies might exist. We developed a novel assay to measure gene copy number and found an average of three additional copies of the CYP2A6 gene. The CYP2A6 gene copy number was significantly correlated with nicotine and cotinine pharmacokinetic parameters as well as with smoking behaviours, indicating that the additional copies are functional and may increase smoking. Furthermore, a 1436G>T variant was identified in all additional CYP2A61xN copies, in some people, using a novel genotyping assay. A genotyping assay for the identification of the putative duplication product (CYP2A612Dup) reciprocal to the CYP2A612 deletion variant was also developed but the CYP2A612Dup was not found. Our results suggest that individuals with multiple functional CYP2A6 genes will have faster nicotine metabolism, greater smoking and possibly greater risk for tobacco-related illnesses.
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Characterization of duplication variants in the CYP2A6 gene.
2005
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0494022744 9780494022740
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Characterization of duplication variants in the CYP2A6 gene.
2005
in English
0494022744 9780494022740
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Edition Notes
Thesis (M.Sc.)--University of Toronto, 2005.
Electronic version licensed for access by U. of T. users.
Source: Masters Abstracts International, Volume: 44-01, page: 0326.
GERSTEIN MICROTEXT copy on microfiche (2 microfiches).
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