| abstract |
Described are general means and methods of diagnosing and treating the phenotypicnspectrum as well as the overlapping clinical characteristics with several forms ofninherited abnormal expression and/or function of the CYP3A4, CYP3A7 and hPXRngenes. In particular, polynucleotides of molecular variant CYP3A4, CYP3A7 and hPXRngenes which, for example, are associated with insufficient metabolization and/ornsensitivety of drugs, and vectors comprising such polynucleotides are provided.nFurthermore, host cells comprising such polynucleotides or vectors and their use fornthe production of variant CYP3A4, CYP3A7 and hPXR proteins are described. Innaddition, variant CYP3A4, CYP3A7 and hPXR proteins and antibodies specificallynrecognizing such proteins as well as transgenic non-human animals comprising thenabove-described polynucleotide or vectors are provided. Described are also methodsnfor identifying and obtaining inhibitors for therapy of disorders related to thenmalfunction of the CYP3A4, CYP3A7 and hPXR genes as well as methods ofndiagnosing the status of such disorders. Pharmaceutical and diagnostic compositionsncomprising the above-described polynucleotides, vectors, proteins, antibodies andninhibitors by the above-described method are provided. Said compositions arenparticularly useful for diagnosing and treating various diseases with drugs that arensubstrates, inhibitors or modulators of the CYP3A4, CYP3A7 or hPXR gene product. |