Abstract
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 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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