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The Making of a CYP3A Biomarker Panel for Guiding Drug Therapy
Program in Pharmacogenomics, Department of Pharmacology, College of Medicine, The Ohio State University, Columbus, OH 43210, USA
* Author to whom correspondence should be addressed.
Received: 20 September 2012; Accepted: 17 October 2012 / Published: 29 October 2012
Abstract: CYP3A ranks among the most abundant cytochrome P450 enzymes in the liver, playing a dominant role in metabolic elimination of clinically used drugs. A main member in CYP3A family, CYP3A4 expression and activity vary considerably among individuals, attributable to genetic and non-genetic factors, affecting drug dosage and efficacy. However, the extent of genetic influence has remained unclear. This review assesses current knowledge on the genetic factors influencing CYP3A4 activity. Coding region CYP3A4 polymorphisms are rare and account for only a small portion of inter-person variability in CYP3A metabolism. Except for the promoter allele CYP3A4*1B with ambiguous effect on expression, common CYP3A4 regulatory polymorphisms were thought to be lacking. Recent studies have identified a relatively common regulatory polymorphism, designated CYP3A4*22 with robust effects on hepatic CYP3A4 expression. Combining CYP3A4*22 with CYP3A5 alleles *1, *3 and *7 has promise as a biomarker predicting overall CYP3A activity. Also contributing to variable expression, the role of polymorphisms in transcription factors and microRNAs is discussed.
Keywords: cytochrome P450s; CYP3A4; polymorphism; biomarker
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Wang, D.; Sadee, W. The Making of a CYP3A Biomarker Panel for Guiding Drug Therapy. J. Pers. Med. 2012, 2, 175-191.
Wang D, Sadee W. The Making of a CYP3A Biomarker Panel for Guiding Drug Therapy. Journal of Personalized Medicine. 2012; 2(4):175-191.
Wang, Danxin; Sadee, Wolfgang. 2012. "The Making of a CYP3A Biomarker Panel for Guiding Drug Therapy." J. Pers. Med. 2, no. 4: 175-191.