Pharmacogenetics of CYP1A2 activity and inducibility in smokers and exsmokers.

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State: Public
Version: author
Serval ID
serval:BIB_DE23A122EB32
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Pharmacogenetics of CYP1A2 activity and inducibility in smokers and exsmokers.
Journal
Pharmacogenetics and Genomics
Author(s)
Dobrinas M., Cornuz J., Eap C.B.
ISSN
1744-6880 (Electronic)
ISSN-L
1744-6872
Publication state
Published
Issued date
2013
Peer-reviewed
Oui
Volume
23
Number
5
Pages
286-292
Language
english
Notes
Publication types: Journal ArticlePublication Status: ppublish
Abstract
BACKGROUND: There is a high interindividual variability in cytochrome P4501A2 (CYP1A2) activity and in its inducibility by smoking, only poorly explained by known CYP1A2 polymorphisms. We aimed to study the contribution of other regulatory pathways, including transcription factors and nuclear receptors, toward this variability.
METHODS: CYP1A2 activity was determined by the paraxanthine/caffeine ratio in 184 smokers and in 113 of them who were abstinent for 4 weeks. Participants were genotyped for 22 polymorphisms in 12 genes.
RESULTS: A significant influence on CYP1A2 inducibility was observed for the NR1I3 rs2502815 (P=0.0026), rs4073054 (P=0.029), NR2B1 rs3818740 (P=0.0045), rs3132297 (P=0.036), AhR rs2282885 (P=0.040), rs2066853 (P=0.019), NR1I1 rs2228570 (P=0.037), and NR1I2 rs1523130 (P=0.044) polymorphisms. Among these, the NR1I3 rs2502815 (P=0.0045), rs4073054 (P=0.048), and NR2B1 rs3818740 (P=0.031) also influenced CYP1A2 basal activity.
CONCLUSION: This is the first in-vivo demonstration of the influence of genes involved in CYP1A2 regulatory pathways on its basal activity and inducibility by smoking. These results need to be confirmed by other studies.
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Create date
04/04/2013 15:58
Last modification date
20/08/2019 17:02
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