Genetic polymorphisms affecting drug metabolism: recent advances and clinical aspects.

Though current knowledge of pharmacogenetic factors relevant to drug metabolism is fairly comprehensive and this should facilitate translation to the clinic, there are a number of gaps in knowledge. Recent studies using both conventional and novel approaches have added to our knowledge of pharmacogenetics of drug metabolism. Genome-wide association studies have provided new insights into the major contribution of cytochromes P450 to response to therapeutic agents such as coumarin anticoagulants and clopidogrel as well as to caffeine and nicotine. Recent advances in understanding of factors affecting gene expression, both regulation by transcription factors and by microRNA and epigenetic factors, have added to understanding of variation in expression of genes such as CYP3A4 and CYP2E1. The implementation of testing for pharmacogenetic polymorphisms in prescription of selected anticancer drugs and cardiovascular agents is considered in detail, with current controversies and barriers to implementation of pharmacogenetic testing assessed. Though genotyping for thiopurine methyltransferase is now common prior to prescription of thiopurines, genotyping for other pharmacogenetic polymorphisms prior to drug prescription remains uncommon. However, it seems likely that it will become more widespread as both increased evidence that certain pharmacogenetic tests are valuable and cost-effective and more accessible genotyping methods become available.