It has been well recognized that drug response is complex and determined by not only one gene, but rather by the interplay of multiple gene products. However, studies of combined impact of more than one gene are scarce, limiting the potential for making strong dosing recommendations based on multiple genes. In this issue of Clinical Pharmacology & Therapeutics, Johnson et al. highlight the importance of multigenic approaches for pharmacogenetics research and clinical implementation, using the examples of tricyclic antidepressant (CYP2D6/CYP2C19) and warfarin (VKORC1/CYP2C9). The authors recommend investigators to conduct “studies in the context of well-defined pharmacogenetic markers, so that the additional impact of the new gene can be placed in the context of the existing pharmacogenetics literature for that drug. More important, it suggests that discoveries of additional pharmacogenes may actually be enhanced by consideration of known pharmacogenetic markers”.
Johnson JA, Klein TE, Relling MV. Clin Pharmacol Ther. 2013 May;93(5):384-5. doi: 10.1038/clpt.2013.7.