View : 20 Download: 0

A common 5′-UTR variant in MATE2-K is associated with poor response to metformin

Title
A common 5′-UTR variant in MATE2-K is associated with poor response to metformin
Authors
Choi J.H.Yee S.W.Ramirez A.H.Morrissey K.M.Jang G.H.Joski P.J.Mefford J.A.Hesselson S.E.Schlessinger A.Jenkins G.Castro R.A.Johns S.J.Stryke D.Sali A.Ferrin T.E.Witte J.S.Kwok P.-Y.Roden D.M.Wilke R.A.McCarty C.A.Davis R.L.Giacomini K.M.
Ewha Authors
최지하
SCOPUS Author ID
최지하scopus
Issue Date
2011
Journal Title
Clinical Pharmacology and Therapeutics
ISSN
0009-9236JCR Link
Citation
vol. 90, no. 5, pp. 674 - 684
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
Multidrug and toxin extrusion 2 (MATE2-K (SLC47A2)), a polyspecific organic cation exporter, facilitates the renal elimination of the antidiabetes drug metformin. In this study, we characterized genetic variants of MATE2-K, determined their association with metformin response, and elucidated their impact by means of a comparative protein structure model. Four nonsynonymous variants and four variants in the MATE2-K basal promoter region were identified from ethnically diverse populations. Two nonsynonymous variantsc.485CT and c.1177GAwere shown to be associated with significantly lower metformin uptake and reduction in protein expression levels. MATE2-K basal promoter haplotypes containing the most common variant, g.130GA (26% allele frequency), were associated with a significant increase in luciferase activities and reduced binding to the transcriptional repressor myeloid zinc finger 1 (MZF-1). Patients with diabetes who were homozygous for g.130A had a significantly poorer response to metformin treatment, assessed as relative change in glycated hemoglobin (HbA1c) (0.027 (0.076, 0.033)), as compared with carriers of the reference allele, g.130G (0.15 (0.17, 0.13)) (P = 0.002). Our study showed that MATE2-K plays a role in the antidiabetes response to metformin. © 2011 American Society for Clinical Pharmacology and Therapeutics.
DOI
10.1038/clpt.2011.165
Appears in Collections:
의과대학 > 의학과 > Journal papers
Files in This Item:
There are no files associated with this item.
Export
RIS (EndNote)
XLS (Excel)
XML


qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

BROWSE