0 65

Cited 0 times in

Functional characterization of MATE2-K genetic variants and their effects on metformin pharmacokinetics

Authors
 Chung, Jae-Yong  ;  Cho, Sung Kweon  ;  Kim, Tae Hee  ;  Kim, Kyoung Hee  ;  Jang, Geun Hye  ;  Kim, Choon Ok  ;  Park, Eun-Mi  ;  Cho, Joo-Youn  ;  Jang, In-Jin  ;  Choi, Ji Ha 
Citation
 Pharmacogenetics and Genomics, Vol.23(7) : 365-373, 2013 
Journal Title
 Pharmacogenetics and Genomics 
ISSN
 1744-6872 
Issue Date
2013
MeSH
Asian Continental Ancestry Group ; Genetic Variation* ; Haplotypes ; Homozygote ; Humans ; Hypoglycemic Agents/pharmacokinetics* ; Metformin/pharmacokinetics* ; Organic Cation Transport Proteins/genetics* ; Polymorphism, Genetic ; Promoter Regions, Genetic
Abstract
OBJECTIVE: Human multidrug and toxin extrusion member 2 (MATE2-K, SLC47A2) plays an important role in the renal elimination of various clinical drugs including the antidiabetic drug metformin. The goal of this study was to characterize genetic variants of MATE2-K and determine their association with the pharmacokinetics of metformin. METHODS: We screened DNA samples from 48 healthy Koreans for variants in the promoter and coding regions of MATE2-K and examined the function of common haplotypes in the promoter region using in-vitro luciferase assays. Then, the metformin pharmacokinetic study was carried out to determine the association between MATE2-K promoter haplotypes and metformin pharmacokinetics. RESULTS: Nine variants in the promoter region of MATE2-K and one nonsynonymous variant, p.G211V, were identified. The MATE2-K promoter haplotype 1 containing a known functional polymorphism, g.-130G>A and haplotype 2 containing two polymorphisms, g.-609G>A and g.-396G>A showed a significant increase in reporter activity. Among the 45 individuals who participated in the metformin pharmacokinetic study, 12 healthy Koreans who were homozygous for haplotype 1 or 2 showed a significant increase in renal clearance [539 ± 76 (reference group) vs. 633 ± 102 (variant group) ml/min; P=0.006] and secretion clearance [439 ± 81 (reference group) vs. 531 ± 102 (variant group) ml/min; P=0.007] of metformin compared with that shown by the reference group. CONCLUSION: Our study suggests that common promoter haplotypes of MATE2-K are associated with the pharmacokinetics of metformin.
Full Text
http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&AN=01213011-201307000-00005&LSLINK=80&D=ovft
DOI
10.1097/FPC.0b013e3283622037
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers
Yonsei Authors
Kim, Choon Ok(김춘옥) ORCID logo https://orcid.org/0000-0002-2319-1108
Cho, Sung Kweon(조성권)
Export
RIS (EndNote)
XLS (Excel)
XML
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/165025
사서에게 알리기
  feedback

qrcode

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

Browse