RT Journal Article SR Electronic T1 Interindividual Variability and Tissue-Specificity in the Expression of Cytochrome P450 3A mRNA JF Drug Metabolism and Disposition JO Drug Metab Dispos FD American Society for Pharmacology and Experimental Therapeutics SP 1108 OP 1114 DO 10.1124/dmd.30.10.1108 VO 30 IS 10 A1 Ina Koch A1 Regina Weil A1 Renzo Wolbold A1 Jürgen Brockmöller A1 Elisabeth Hustert A1 Oliver Burk A1 Andreas Nuessler A1 Peter Neuhaus A1 Michel Eichelbaum A1 Ulrich Zanger A1 Leszek Wojnowski YR 2002 UL http://dmd.aspetjournals.org/content/30/10/1108.abstract AB The elucidation of the individual contributions of the fourCYP3A genes to the overall CYP3A activity has been hampered by similarities in their sequence and function. We investigated the expression of CYP3A mRNA species in the liver and in various other tissues using gene-specific TaqMan probes. CYP3A4 transcripts were the most abundant CYP3A mRNA in each of the 63 white European livers tested and accounted on average for 95% of the combined CYP3A mRNA pool. CYP3A5 and CYP3A7 each contributed on average 2%, whereas CYP3A43 contributed 0.3% transcripts to this pool. Fourteen percent of livers exhibited an increased share of CYP3A5 transcripts (range 4–20%). These livers were either heterozygous for the marker of the CYP3A5 polymorphism, the CYP3A5*1A allele, or expressed very low levels of CYP3A4 mRNA. The CYP3A7 expression was bimodal, and it was increased in 15% livers. CYP3A4 was the dominant CYP3A in the intestine, followed by CYP3A5. CYP3A5 and CYP3A7, but not CYP3A4, were also expressed in the adrenal gland and in the prostate, whereas only CYP3A5 was detected in the kidney. These three tissues were shown to express much lower levels of pregnane X receptor mRNA than the intestine, indicating possibly a different mode of regulation of CYP3A expression. Expression of CYP3A genes was undetectable in peripheral blood lymphocytes. In summary, these assays and results should aid in our efforts to further dissect the regulation and the physiological and pharmacological significance of CYP3A isozymes. The American Society for Pharmacology and Experimental Therapeutics