Pharmacogenetics of metformin response: a step in the path toward personalized medicine
J. Clin. Invest. Marc L. Reitman, et al. 117:1226 doi:10.1172/JCI32133 [Go to this article.]

Figure 1
Elucidating the complexity of drug response. (A) A classical pharmacogenetic approach to identifying genes associated with drug response involves testing DNA variations in candidate genes for association to drug response. Variations in cytochrome P450s and drug targets such as VKORC1 (target of warfarin) have been identified that explain variation in drug response. Individual genotypes corresponding to such variations can be used to distinguish responders from nonresponders or rapid from slow metabolizers or those at risk of adverse events. (B) Pharmacogenomic studies involve larger-scale genome-wide association approaches or the integration of a diversity of genetic, functional genomic, and other data to elucidate the complexity of drug response. In this issue of the JCI, Shu et al. (4) employed cell-based experiments, in vivo studies in mice, and in vivo human trials to identify OCT1 as a gene associated with response to treatment with metformin. The use of multiple experimental approaches provided more convincing results than could a single genetic study in implicating OCT1 as a metformin response gene.