Journal article
Pharmacogenetics of CYP1A2 activity and inducibility in smokers and exsmokers.
- Dobrinas M Unit of Pharmacogenetics and Clinical Psychopharmacology, Department of Psychiatry, Centre for Psychiatric Neurosciences, Lausanne University Hospital, Prilly, Lausanne, Switzerland.
- Cornuz J
- Eap CB
- 2013-03-16
Published in:
- Pharmacogenetics and genomics. - 2013
Adult
Caffeine
Cytochrome P-450 CYP1A2
Female
Genotype
Humans
Male
Pharmacogenetics
Phenotype
Polymorphism, Single Nucleotide
Pregnane X Receptor
Receptors, Aryl Hydrocarbon
Receptors, Cytoplasmic and Nuclear
Receptors, Steroid
Smoking
English
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.
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.
- Language
-
- English
- Open access status
- closed
- Identifiers
-
- DOI 10.1097/FPC.0b013e3283602e75
- PMID 23492909
- Persistent URL
- https://folia.unifr.ch/global/documents/122964
Statistics
Document views: 8
File downloads: