Pharmacogenomics of Human Multidrug Resistance Associated Proteins

Abstract

Inter-individual variations in response to pharmacotherapy such as adverse effects, treatment resistance and toxicities affect all patient populations. Multidrug resistance associated proteins (MRPs) work as efflux pumps for many xenobiotics and endogenous substances and hence, can affect the drug concentration at the target site which governs therapeutic response. Genetic polymorphisms of the MRPs can lead to an over- or under-expression of these transporter proteins. These polymorphisms can therefore play an integral role in drug disposition and therapeutic outcomes via pharmacokinetic and pharmacodynamic changes. These changes may cause drug-drug interactions, treatment resistance and/or toxicity. Overexpression of certain MRPs is thought to correlate with multidrug resistance in pharmacotherapy, especially with anticancer drugs. It is also evident that some genetic variants linked with MRP genes can lead to disease states such as pseudoxanthoma elasticum. With further research, more definitive functional characterization of MRPs and the understanding of this relationship with genetic polymorphisms can be achieved. This article highlights the genetic polymorphisms of MRPs and their clinical implications with an emphasis on MRP1-4. It also provides an insight into the role that these proteins can play in disease states and toxicities as well as the implications for future research and patient management.