The Impact of Genetic Polymorphisms in Organic Cation Transporters on Renal Drug Disposition

• Main Authors: Zulfan Zazuli, Naut J. C. B. Duin, Katja Jansen, Susanne J. H. Vijverberg, Anke H. Maitland-van der Zee, Rosalinde Masereeuw
• Format: Article
• Language: English
• Published: MDPI AG 2020-09-01
• Series: International Journal of Molecular Sciences
• Subjects: organic cation transporters; drug disposition; genetic polymorphisms; kidney; drug-induced kidney injury; nephrotoxicity
• Online Access: https://www.mdpi.com/1422-0067/21/18/6627
• ISSN: 1661-6596; 1422-0067

A considerable number of drugs and/or their metabolites are excreted by the kidneys through glomerular filtration and active renal tubule secretion via transporter proteins. Uptake transporters in the proximal tubule are part of the solute carrier (SLC) superfamily, and include the organic cation transporters (OCTs). Several studies have shown that specific genetic polymorphisms in OCTs alter drug disposition and may lead to nephrotoxicity. Multiple single nucleotide polymorphisms (SNPs) have been reported for the OCT genes (<i>SLC22A1</i>, <i>SLC22A2</i> and <i>SLC22A3</i>), which can influence the proteins’ structure and expression levels and affect their transport function. A gain-in-function mutation may lead to accumulation of drugs in renal proximal tubule cells, eventually leading to nephrotoxicity. This review illustrates the impact of genetic polymorphisms in OCTs on renal drug disposition and kidney injury, the clinical significances and how to personalize therapies to minimize the risk of drug toxicity.