Analysis of regulatory polymorphisms in organic ion transporter genes (SLC22A) in the kidney.

Journal of Human Genetics
Ken OgasawaraK Inui

Abstract

Organic cation transporters (OCTs) and organic anion transporters (OATs) (SLC22A family) play crucial roles in the renal secretion of various drugs. Messengar ribonucleic acid (mRNA) expression of transporters can be a key factor regulating interindividual differences in drug pharmacokinetics. However, the source of variations in mRNA levels of transporters is unclear. In this study, we focused on single nucleotide polymorphisms (SNP) in the promoter region [regulatory SNPs (rSNPs)] as candidates for the factor regulating mRNA levels of SLC22A. We sequenced the promoter regions of OCT2 and OAT1-4 in 63 patients and investigated the effects of the identified rSNPs on transcriptional activities and mRNA expression. In the OCT2 promoter region, one deletion polymorphism (-578_-576delAAG) was identified; -578_-576delAAG significantly reduced OCT2 promoter activity (p < 0.05), and carriers of -578_-576delAAG tend to have lower OCT2 mRNA levels, but the difference is not significant. There was no rSNP in the OAT1 and OAT2 genes. The five rSNPs of OAT3 and one rSNP of OAT4 were unlikely to influence mRNA expression and promoter activity. This is the first study to investigate the influences of rSNPs on mRNA expression of SLC22A in the...Continue Reading

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Citations

Jun 2, 2009·Pharmacogenetics and Genomics·Ying ChenKathleen M Giacomini
Jan 15, 2009·The Journal of Pharmacology and Experimental Therapeutics·Harunobu TaharaKathleen M Giacomini
May 28, 2010·Pharmacogenomics·Ekaitz Errasti-Murugarren, Marçal Pastor-Anglada
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Jul 31, 2012·Pharmacology & Therapeutics·Gerhard Burckhardt
Dec 21, 2012·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Chang-Ik ChoiSeok-Yong Lee
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Jun 21, 2016·Advanced Drug Delivery Reviews·Fanfan ZhouMichael Murray
Apr 7, 2018·Drug Metabolism and Personalized Therapy·Brendon PearceMongi Benjeddou
Apr 17, 2018·Journal of Personalized Medicine·Elisa LozanoElisa Herraez
Jul 15, 2015·The Korean Journal of Physiology & Pharmacology : Official Journal of the Korean Physiological Society and the Korean Society of Pharmacology·Seong Kyu AhnSeok Ho Cha
Jul 22, 2009·Pharmacogenetics and Genomics·Masayo AokiKen-Ichi Inui
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Jan 19, 2011·Clinical Pharmacokinetics·Garry G GrahamKenneth M Williams
Dec 14, 2018·Journal of Personalized Medicine·Kristin BokelmannMladen V Tzvetkov

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