Genetic and/or non-genetic causes for inter-individual and inter-cellular variability in transporter protein expression: implications for understanding drug efficacy and toxicity.
BACKGROUND
Drug transporters are differentially expressed in many polarized tissues. The varied distribution and expression of transporters determines the net transcellular transport and influences the disposition of many clinically used drugs. ATP-binding cassette (ABC) and Solute Carrier (SLC) transporters interact dynamically to mediate the passage of drugs across cells. The variable expression of drug transporters could be attributed to genetic and non-genetic factors, which accounts for the differences in drug response among individuals, in terms of both efficacy and adverse effects.


METHODS
The authors provide the background of ABC and SLC transporters, and highlight the fact that their expression is cell-specific and the study of a transporter in isolation is not an adequate measure of its function. The technologies and approaches to characterize the function of transporters, as well as the genetic and non-genetic factors underlying their variable expression in specific cells and among individuals were reviewed.


CONCLUSIONS
Many studies have utilized tissue homogenization techniques to isolate mRNA for quantifying transporter expression levels. We highlight that transporter expression is cell-specific and mRNA expression does not always reflect its total functionality. In addition, transporter expression in immortalized cell lines may not mirror its expression in the target tissue site.
a Department of Pharmacology, Yong Loo Lin School of Medicine , National University of Singapore , Singapore , Singapore.|b Clinical Trials & Research Unit , Changi General Hospital , Singapore , Singapore.
Seok Hwee
SH
Koo
a Department of Pharmacology, Yong Loo Lin School of Medicine , National University of Singapore , Singapore , Singapore.
Ying Li
YL
Lo
a Department of Pharmacology, Yong Loo Lin School of Medicine , National University of Singapore , Singapore , Singapore.
Jie Yin
JY
Yee
a Department of Pharmacology, Yong Loo Lin School of Medicine , National University of Singapore , Singapore , Singapore.
Edmund Jon Deoon
EJ
Lee
D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport / Q000235:genetics; D064420:Drug-Related Side Effects and Adverse Reactions / Q000209:etiology* / Q000235:genetics; D005786:Gene Expression Regulation; D006801:Humans; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D004364:Pharmaceutical Preparations / Q000008:administration & dosage / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism
D018528:ATP-Binding Cassette Transporters; D026901:Membrane Transport Proteins; D004364:Pharmaceutical Preparations; D012333:RNA, Messenger
drug transporters; efficacy; epigenetics; genetics; toxicity; variable expression