Genetics of the variable expression of CYP3A in humans.
CYP3A isozymes participate in the metabolism of 45-60% of currently used drugs and of a variety of other compounds such as steroid hormones, toxins, and carcinogens. The CYP3A expression status is a major determinant of drug efficacy and safety, and it may also affect an individual's predisposition to certain cancers. The inter- and intraindividual expression of CYP3A is variable because of a complex interplay between genetic and environmental factors. Markers predictive of the individual CYP3A activity could improve therapies with CYP3A substrates by personalised dose adjustments, but their development has been slower than for other drug-metabolizing enzymes. Here we summarize the recent progress in genomics and regulation of CYP3A. The recently described markers of the CYP3A5 and CYP3A7 polymorphisms should facilitate the development of isozyme-specific activity markers for the individual CYP3A isozymes, including CYP3A4.
Wojnowski
Leszek
L
Department of Clinical Pharmacology, Johannes Gutenberg University, D-55101 Mainz, Germany. wojnowski@uni-mainz.de
D001189:Aryl Hydrocarbon Hydroxylases / Q000096:biosynthesis / Q000235:genetics*; D051544:Cytochrome P-450 CYP3A; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D009928:Organ Specificity; D010089:Oxidoreductases, N-Demethylating / Q000096:biosynthesis / Q000235:genetics*; D004364:Pharmaceutical Preparations / Q000378:metabolism; D010599:Pharmacokinetics; D011110:Polymorphism, Genetic / Q000235:genetics
D004364:Pharmaceutical Preparations; D001189:Aryl Hydrocarbon Hydroxylases; D051544:Cytochrome P-450 CYP3A; D010089:Oxidoreductases, N-Demethylating