Identification and functional characterization of novel MATE1 genetic variations in Koreans

Tae Hee Kim; Kyoung Hee Kim; Hyo Jin Park; Siyoon Kim; Ji Ha Choi

doi:10.1016/j.bbrc.2013.03.072

Identification and functional characterization of novel MATE1 genetic variations in Koreans

Tae Hee Kim, Kyoung Hee Kim, Hyo Jin Park, Siyoon Kim, Ji Ha Choi

Department of Pharmacology

Research output: Contribution to journal › Article › peer-review

8 Scopus citations

Abstract

Multidrug and toxin extrusion 1 (MATE1, SLC47A1), an organic cation transporter, plays an important role in the renal and biliary elimination of various clinical drugs, including the anti-diabetic drug metformin. The goal of this study was to identify and characterize novel genetic variants of MATE1. Five variants in the promoter region and two nonsynonymous variants, p.D64G and p.L125F, were identified in 48 DNA samples from healthy Koreans. MATE1 promoter haplotype 3 containing g.-1975C>A showed a significant increase in reporter activity. Three transcription factors, Nkx-2.5, SREBP-1, and USF-1 were predicted to bind to the promoter in the region of g.-1975C>A. Results from electrophoretic mobility shift assays showed that the g.-1975A allele exhibits greater binding affinity to all of these transcription factors than the g.-1975C allele. In particular, we found that Nkx-2.5 and USF-1 induce MATE1 transcription. Our study suggests that the common promoter haplotype of MATE1 changes MATE1 transcriptional activity regulated by Nkx-2.5, SREBP-1, and USF-1.

Original language	English
Pages (from-to)	334-340
Number of pages	7
Journal	Biochemical and Biophysical Research Communications
Volume	434
Issue number	2
DOIs	https://doi.org/10.1016/j.bbrc.2013.03.072
State	Published - 3 May 2013

Keywords

Haplotype
MATE1
Nkx-2.5
Promoter
SREBP-1
USF-1

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10.1016/j.bbrc.2013.03.072

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@article{2356d6bbadea4c63a9ddd9f03b9600d2,

title = "Identification and functional characterization of novel MATE1 genetic variations in Koreans",

abstract = "Multidrug and toxin extrusion 1 (MATE1, SLC47A1), an organic cation transporter, plays an important role in the renal and biliary elimination of various clinical drugs, including the anti-diabetic drug metformin. The goal of this study was to identify and characterize novel genetic variants of MATE1. Five variants in the promoter region and two nonsynonymous variants, p.D64G and p.L125F, were identified in 48 DNA samples from healthy Koreans. MATE1 promoter haplotype 3 containing g.-1975C>A showed a significant increase in reporter activity. Three transcription factors, Nkx-2.5, SREBP-1, and USF-1 were predicted to bind to the promoter in the region of g.-1975C>A. Results from electrophoretic mobility shift assays showed that the g.-1975A allele exhibits greater binding affinity to all of these transcription factors than the g.-1975C allele. In particular, we found that Nkx-2.5 and USF-1 induce MATE1 transcription. Our study suggests that the common promoter haplotype of MATE1 changes MATE1 transcriptional activity regulated by Nkx-2.5, SREBP-1, and USF-1.",

keywords = "Haplotype, MATE1, Nkx-2.5, Promoter, SREBP-1, USF-1",

author = "Kim, {Tae Hee} and Kim, {Kyoung Hee} and Park, {Hyo Jin} and Siyoon Kim and Choi, {Ji Ha}",

note = "Funding Information: This study was supported by grant of the National Project for Personalized Genomic Medicine, Ministry for Health & Welfare , Republic of Korea [ A111218-PG03 ], the National Research Foundation (NRF) grant funded by the Korea government (MEST) [ 2012-0009844 ], and the Ewha Womans University Research Grant of 2009 . We thank Dr. I. Jang and Dr. J. Cho for their help in obtaining genomic DNA samples from the DNA bank of the Korea Pharmacogenomics Research Network at Seoul National University. We also thank Dr. J. Chung for his help in retrospective analysis of DNA samples from metformin pharmacokinetic study.",

year = "2013",

month = may,

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doi = "10.1016/j.bbrc.2013.03.072",

language = "English",

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pages = "334--340",

journal = "Biochemical and Biophysical Research Communications",

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T1 - Identification and functional characterization of novel MATE1 genetic variations in Koreans

AU - Kim, Tae Hee

AU - Kim, Kyoung Hee

AU - Park, Hyo Jin

AU - Kim, Siyoon

AU - Choi, Ji Ha

N1 - Funding Information: This study was supported by grant of the National Project for Personalized Genomic Medicine, Ministry for Health & Welfare , Republic of Korea [ A111218-PG03 ], the National Research Foundation (NRF) grant funded by the Korea government (MEST) [ 2012-0009844 ], and the Ewha Womans University Research Grant of 2009 . We thank Dr. I. Jang and Dr. J. Cho for their help in obtaining genomic DNA samples from the DNA bank of the Korea Pharmacogenomics Research Network at Seoul National University. We also thank Dr. J. Chung for his help in retrospective analysis of DNA samples from metformin pharmacokinetic study.

PY - 2013/5/3

Y1 - 2013/5/3

N2 - Multidrug and toxin extrusion 1 (MATE1, SLC47A1), an organic cation transporter, plays an important role in the renal and biliary elimination of various clinical drugs, including the anti-diabetic drug metformin. The goal of this study was to identify and characterize novel genetic variants of MATE1. Five variants in the promoter region and two nonsynonymous variants, p.D64G and p.L125F, were identified in 48 DNA samples from healthy Koreans. MATE1 promoter haplotype 3 containing g.-1975C>A showed a significant increase in reporter activity. Three transcription factors, Nkx-2.5, SREBP-1, and USF-1 were predicted to bind to the promoter in the region of g.-1975C>A. Results from electrophoretic mobility shift assays showed that the g.-1975A allele exhibits greater binding affinity to all of these transcription factors than the g.-1975C allele. In particular, we found that Nkx-2.5 and USF-1 induce MATE1 transcription. Our study suggests that the common promoter haplotype of MATE1 changes MATE1 transcriptional activity regulated by Nkx-2.5, SREBP-1, and USF-1.

AB - Multidrug and toxin extrusion 1 (MATE1, SLC47A1), an organic cation transporter, plays an important role in the renal and biliary elimination of various clinical drugs, including the anti-diabetic drug metformin. The goal of this study was to identify and characterize novel genetic variants of MATE1. Five variants in the promoter region and two nonsynonymous variants, p.D64G and p.L125F, were identified in 48 DNA samples from healthy Koreans. MATE1 promoter haplotype 3 containing g.-1975C>A showed a significant increase in reporter activity. Three transcription factors, Nkx-2.5, SREBP-1, and USF-1 were predicted to bind to the promoter in the region of g.-1975C>A. Results from electrophoretic mobility shift assays showed that the g.-1975A allele exhibits greater binding affinity to all of these transcription factors than the g.-1975C allele. In particular, we found that Nkx-2.5 and USF-1 induce MATE1 transcription. Our study suggests that the common promoter haplotype of MATE1 changes MATE1 transcriptional activity regulated by Nkx-2.5, SREBP-1, and USF-1.

KW - Haplotype

KW - MATE1

KW - Nkx-2.5

KW - Promoter

KW - SREBP-1

KW - USF-1

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DO - 10.1016/j.bbrc.2013.03.072

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SN - 0006-291X

VL - 434

SP - 334

EP - 340

JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

IS - 2

ER -

Identification and functional characterization of novel MATE1 genetic variations in Koreans

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Keywords

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