OBJECTIVE: The aim of pharmacogenomics is to identify individual differences in 
genome and transcriptome composition and their effect on drug efficacy. 
MicroRNAs (miRNAs) are short noncoding RNAs that negatively regulate expression 
of the majority of animal genes, including many genes involved in drug efficacy. 
Consequently, differences in the miRNA expression among individuals could be an 
important factor contributing to differential drug response. Pharmacogenomics 
genes can be divided into drug target genes termed as pharmacodynamics genes 
(PD) and genes involved in drug transport and metabolism termed as 
pharmacokinetics genes (PK). To clarify the regulatory potential of miRNAs in 
pharmacogenomics, we have examined the potential regulation by miRNAs of PK and 
PD genes.
METHODS: We identified PK and PD genes as annotated by the Pharmacogenomics 
Knowledge Base and examined miRNA targeting of genes in the two groups according 
to several miRNA target prediction databases. We furthermore studied how 
differences between the two groups are reflected in the gene structure and 
across gene families. Lastly, we studied changes in expression levels of PK 
versus PD genes in cells depleted for miRNAs by shRNA-mediated knockdown of the 
miRNA-processing enzyme Dicer.
RESULTS: Our analysis identify a striking difference in the level of miRNA 
regulation between PK and PD genes, with the former having less than half 
predicted conserved miRNA binding sites compared with the latter. Importantly, 
this finding is reflected in a highly significant difference in the shift in 
expression levels of PD versus PK genes after depletion of miRNAs.
CONCLUSION: Our study emphasizes an intrinsic difference between PK and PD genes 
and helps clarify the role of miRNAs in pharmacogenomics.