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| Ewha Med J. 2011 Mar;34(1):9-13. Korean. Published online March 31, 2011. https://doi.org/10.12771/emj.2011.34.1.9 | |
| Copyright © 2011. Ewha Womans University School of Medicine | |
Ji Ha Choi
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| Department of Pharmacology, School of Medicine, Ewha Womans University, Korea. | |
| Corresponding author (
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This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by- | |
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Abstract
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Objectives
Human organic cation transporter 2, OCT2(SLC22A2), highly expressed on the renal proximal tubular cells, plays an important role in the renal excretion of endogenous and exogenous organic cations including many therapeutic drugs. This study was performed to identify genetic variations in the proximal promoter region of OCT2.
Methods
The promoter region of OCT2 was amplified and directly sequenced from genomic DNA samples from individuals of diverse ethnicities(n=272). The promoter activity of OCT2 was measured using a luciferase reporter assay in two cell lines ; ACHN, and HCT-116.
Results
There were four polymorphic(minor allele frequency >1% in at least one of the four ethnic groups) variants in the OCT2 promoter region(-250/+60 from the transcription start site). One(V2, g.-246C>T) of them showed decreased reporter activity by 38%(p<0.001), whereas another one(V4, g.-47C>T) showed increased activity by 10%(p<0.05), compared to the reference in HCT-116 cell line.
Conclusion
This study revealed that novel promoter variants of OCT2 results in changes in transcriptional activity of this gene. These variants can potentially affect the pharmacokinetics or drug response of many drugs that are substrates of OCT2. |
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Keywords: OCT2; Genetic variation; Promoter; Transporter |
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