TY - JOUR
T1 - The impact of genetic polymorphisms in organic cation transporters on renal drug disposition
AU - Zazuli, Zulfan
AU - Duin, Naut J. C. B.
AU - Jansen, Katja
AU - Vijverberg, Susanne J. H.
AU - Maitland-van der Zee, Anke H.
AU - Masereeuw, Rosalinde
PY - 2020/9/2
Y1 - 2020/9/2
N2 - 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 (SLC22A1, SLC22A2 and SLC22A3), 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.
AB - 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 (SLC22A1, SLC22A2 and SLC22A3), 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.
KW - Drug disposition
KW - Drug-induced kidney injury
KW - Genetic polymorphisms
KW - Kidney
KW - Nephrotoxicity
KW - Organic cation transporters
UR - http://www.scopus.com/inward/record.url?scp=85090642799&partnerID=8YFLogxK
U2 - https://doi.org/10.3390/ijms21186627
DO - https://doi.org/10.3390/ijms21186627
M3 - Review article
C2 - 32927790
SN - 1661-6596
VL - 21
SP - 1
EP - 23
JO - International journal of molecular sciences
JF - International journal of molecular sciences
IS - 18
M1 - 6627
ER -