The impact of microRNAs and alternative splicing in pharmacogenomics

Pharmacogenomic studies emphasize the use of genomic information to enhance success in finding new medicines and also to improve those that are already used in clinics. Therefore, this field has a special interest in knowing how patients metabolize drugs depending on their genetic background. Most of the studies so far have focused on the impact of single genetic differences on drug metabolism. However, this may be only the tip of the iceberg in terms of how interpatient variability can influence the response to drugs. For example, control of gene expression by microRNAs (miRNAs) and alternative splicing are cellular mechanisms that have an effect on proteome diversity and have already been implicated in complex diseases such as cancer, arthritis and others. Changes in the sequence of a miRNA and/or variations in the miRNA target region of a transcript can have a major impact on post-transcriptional regulation. Events of alternative splicing can occur in more than half of the human genes, thereby changing the sequence of key proteins related to drug resistance, activation and metabolism. Furthermore, alternative splicing and miRNAs can work together to differentially control genes. This perspective article will highlight recent exciting discoveries in pharmacogenomics and also discuss how players such as miRNAs and alternative splicing may affect the way we design and apply future therapies.