Original ArticlesGenomic organization of the human CYP3A locus: identification of a new, inducible CYP3A geneGellner, Klausa; Eiselt, Reginaa; Hustert, Elisabetha; Arnold, Hannesa; Koch, Inaa; Haberl, Michaela; Deglmann, Claus J.b; Burk, Oliverc; Buntefuss, Danielaa; Escher, Stephaniea; Bishop, Cheryla; Koebe, Hans-Günterb; Brinkmann, Ulricha; Klenk, Hans-Petera; Kleine, Karla; Meyer, Urs A.d; Wojnowski, LeszekaAuthor Information aEpidauros Biotechnologie AG, Bernried, Germany, bDepartment of Surgery, Klinikum Grosshadern, Ludwig-Maximilians-University of Munich, Germany, cDr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany, dDivision of Pharmacology/Neurobiology, Biozentrum, University of Basel, Switzerland Received 26 June 2000; accepted 4 October 2000 Correspondence to Leszek Wojnowski, Epidauros Biotechnologie AG, Am Neuland 1, 82347 Bernried, Germany Tel: +49 8158 99 85 76; fax: +49 8158 99 85 48; e-mail: [email protected] *The name of the gene has been adopted from an independent assembly of the gene protein sequence by D. Nelson and H. Strobel (http://drnelson.utem.edu/Human.new.html). Pharmacogenetics: March 2001 - Volume 11 - Issue 2 - p 111-121 Buy Abstract Proteins encoded by the human CYP3A genes metabolize every second drug currently in use. The activity of CYP3A gene products in the general population is highly variable and may affect the efficacy and safety of drugs metabolized by these enzymes. The mechanisms underlying this variability are poorly understood, but they include gene induction, protein inhibition and unknown genetic polymorphisms. To better understand the regulation of CYP3A expression and to provide a basis for a screen of genetic polymorphisms, we determined and analysed the sequence of the human CYP3A locus. The 231 kb locus sequence contains the three CYP3A genes described previously (CYP3A4, CYP3A5 and CYP3A7), three pseudogenes as well as a novel CYP3A gene termed CYP3A43. The gene encodes a putative protein with between 71.5% and 75.8% identity to the other CYP3A proteins. The highest expression level of CYP3A43 mRNA is observed in the prostate, an organ with extensive steroid metabolism. CYP3A43 is also expressed in several other tissues including liver, where it can be induced by rifampicin. CYP3A43 transcripts undergo extensive splicing. The identification of a new member of the CYP3A family and the characterization of the full CYP3A locus will aid efforts to identify the genetic variants underlying its variable expression. This, in turn, will lead to a better optimization of therapies involving the numerous substrates of CYP3A proteins. © 2001 Lippincott Williams & Wilkins, Inc.