Format

Send to

Choose Destination
Pharmacogenet Genomics. 2013 Jul;23(7):365-73. doi: 10.1097/FPC.0b013e3283622037.

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

Author information

1
Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Bundang Hospital, Seongnam, Korea.

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.

PMID:
23652408
DOI:
10.1097/FPC.0b013e3283622037
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Wolters Kluwer
Loading ...
Support Center