Transcriptional Regulation of CYP2C19 and its Role in Altered Enzyme Activity
Chakradhara Rao S. Uppugunduri, Youssef Daali, Jules Desmeules, Pierre Dayer, Maja Krajinovic and Marc Ansari
Affiliation: Department of Pediatrics, Onco-hematology unit, Geneva University Hospitals, 1205 Geneva, Switzerland.
Keywords: CYP2C19, transcription, promoter, transcription factor, genetic variants, induction, inhibition, drug interaction, Transcriptional Regulation, Cytochrome P450, PPIs, hydrogen bond acceptors, intermediate metabolizers, extensive metabolizers, endogenous factors, genotype-phenotype association, GRE.
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
Rights & PermissionsPrintExport