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The genetic determinants of the CYP3A5 polymorphism.
Investigation of the expression of CYP3A5 and its genetic determinants in a panel of 183 Caucasian liver samples reports that a SNP within intron 3 (g.6986G>A) is the primary cause of the CYP4A5 protein polymorphism, and should add to efforts to identify clinically relevant, CYP2A5-specific reactions and to further elucidate traits responsible for variable expression of the entire CYP 3A family.
NAD(P)H Oxidase and Multidrug Resistance Protein Genetic Polymorphisms Are Associated With Doxorubicin-Induced Cardiotoxicity
Genetic variants in doxorubicin transport and free radical metabolism may modulate the individual risk to develop ACT.
Rhabdomyosarcomas and radiation hypersensitivity in a mouse model of Gorlin syndrome
- H. Hahn, L. Wojnowski, A. Zimmer, Jennifer Hall, G. Miller, A. Zimmer
- Medicine, BiologyNature Medicine
- 1 May 1998
It is shown that ptc heterozygous mice exhibit increased incidence of radiation-induced teratogenesis, which suggests a role for ptc in the response to ionizing radiation and provides a model for both the systemic and stochastic abnormalities observed in Gorlin syndrome.
Natural protein variants of pregnane X receptor with altered transactivation activity toward CYP3A4.
Three natural PXR protein variants may play a role in the observed interindividual variability of CYP3A4 expression and may be involved in rare, atypical responses to drugs or altered sensitivities to carcinogens.
Interindividual variability and tissue-specificity in the expression of cytochrome P450 3A mRNA.
- I. Koch, R. Weil, L. Wojnowski
- Biology, MedicineDrug metabolism and disposition: the biological…
- 1 October 2002
Investigation of the expression of CYP3A mRNA species in the liver and in various other tissues using gene-specific TaqMan probes should aid in efforts to further dissect the regulation and the physiological and pharmacological significance of CYp3A isozymes.
Identification and functional characterization of eight CYP3A4 protein variants.
A study of 213 Middle and Western European DNA samples resulted in the identification of 18 new CYP3A4 variants, including eight protein variants that may play a role in the atypical response to drugs or altered sensitivity to carcinogens.
Genomic organization of the human CYP3A locus: identification of a new, inducible CYP3A gene.
The identification of a new member of the CYP3A family and the characterization of the full CYP 3A locus will aid efforts to identify the genetic variants underlying its variable expression, which will lead to a better optimization of therapies involving the numerous substrates of CYP2A proteins.
Resveratrol reduces endothelial oxidative stress by modulating the gene expression of superoxide dismutase 1 (SOD1), glutathione peroxidase 1 (GPx1) and NADPH oxidase subunit (Nox4).
The expressional suppression of pro-oxidative genes (such as NADPH oxidase) and induction of anti- oxidative enzymes ( such as SOD1 and GPx1) might be an important component of the vascular protective effect of resveratrol.
Molecular Mechanisms of Polymorphic CYP3A7 Expression in Adult Human Liver and Intestine*
It is concluded that the presence of the ER6 motif of CYP3A4mediates the high expression of CYp3A7 in subjects carrying CYP 3A7*1C.
Endothelial apoptosis in Braf-deficient mice
It is shown that mice with a targeted disruption in the Braf gene die of vascular defects during mid-gestation, and this work provides the first genetic evidence for an essential role of a Raf gene in the regulation of programmed cell death.