Transcriptional regulation and pharmacogenomics

Abstract

Interindividual variable drug response is correlated with sequence alterations in genes encoding drug-metabolizing enzymes and transporters, affecting drug absorption, distribution, metabolism and excretion. This variable drug response may have an impact on disease therapeutic outcomes, tolerance to adverse drug reactions and even survival. Sequence alterations may occur not only within the coding region of a gene, but in its regulatory elements too, affecting gene transcription and gene-expression levels. Here, we provide a compilation of the current knowledge of pharmacogenomics related to transcription, with a focus on the effect of SNPs and short tandem repeats residing in cis-regulatory elements of 11 genes encoding for drug-metabolizing enzymes and drug transporters. In addition, we comment on two genes encoding enzymes that are drug targets themselves. Finally, we briefly discuss the currently available methodologies for clinically assessing pharmacogenomic profiles, which could potentially in the future facilitate drug treatment-individualization via the identification of molecular signatures in specific patient groups.