Transcriptional regulation of CYP2C19 and its role in altered enzyme activity.
Cytochrome P450 2C19 (CYP2C19) is involved in the metabolism of several drugs that are currently in clinical use. The gene encoding CYP2C19 is polymorphic with the existence of different alleles resulting in altered enzyme activity. In addition, CYP2C19 activity is also dependent on its basal expression levels determined by the transcriptional regulation. Genetic variations located in the CYP2C19 promoter region may alter the interaction of promoter with transcription factors causing variable transcription. Genetic variants may also influence the induction, inhibition of CYP2C19 and may as well affect drug-drug interactions involving CYP2C19 substrates. The role of various transcription factors and genetic variants in the promoter region of CYP2C19 regulating its expression are discussed in this review. Furthermore, induction and inhibition of CYP2C19 by various drugs in clinically meaningful drug interactions are also discussed.
Department of Pediatrics, Onco-Hematology Unit, Geneva University Hospitals, 1205 Geneva, Switzerland. Chakradhara.Uppugunduri@unige.ch
Chakradhara Rao S
CR
Uppugunduri
Youssef
Y
Daali
Jules
J
Desmeules
Pierre
P
Dayer
Maja
M
Krajinovic
Marc
M
Ansari
D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics* / Q000378:metabolism; D065731:Cytochrome P-450 CYP2C19; D015971:Gene Expression Regulation, Enzymologic; D014644:Genetic Variation; D006801:Humans; D004364:Pharmaceutical Preparations / Q000378:metabolism; D014158:Transcription, Genetic
D004364:Pharmaceutical Preparations; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19