期刊
PHARMACOGENETICS AND GENOMICS
卷 23, 期 7, 页码 365-373出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/FPC.0b013e3283622037
关键词
genetic variant; haplotype; MATE2-K; metformin; pharmacokinetics; promoter; SLC47A2; transcriptional activity; transporter
资金
- National Project for Personalized Genomic Medicine, Ministry for Health and Welfare, Republic of Korea [A111218-PG03]
- National Research Foundation (NRF)
- Korea government (MEST) [2012-0009844]
- Health Fellowship Foundation
ObjectiveHuman 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.MethodsWe 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.ResultsNine 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 [53976 (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.ConclusionOur study suggests that common promoter haplotypes of MATE2-K are associated with the pharmacokinetics of metformin.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据