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

DC Field Value Language
dc.contributor.author김춘옥-
dc.contributor.author조성권-
dc.date.accessioned2018-11-05T16:40:06Z-
dc.date.available2018-11-05T16:40:06Z-
dc.date.issued2013-
dc.identifier.issn1744-6872-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/165025-
dc.description.abstractOBJECTIVE: 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.-
dc.description.statementOfResponsibilityrestriction-
dc.languageEnglish-
dc.publisherLippincott Williams & Wilkins-
dc.relation.isPartOfPHARMACOGENETICS AND GENOMICS-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.rightshttps://creativecommons.org/licenses/by-nc-nd/2.0/kr/-
dc.subject.MESHAsian Continental Ancestry Group-
dc.subject.MESHGenetic Variation*-
dc.subject.MESHHaplotypes-
dc.subject.MESHHomozygote-
dc.subject.MESHHumans-
dc.subject.MESHHypoglycemic Agents/pharmacokinetics*-
dc.subject.MESHMetformin/pharmacokinetics*-
dc.subject.MESHOrganic Cation Transport Proteins/genetics*-
dc.subject.MESHPolymorphism, Genetic-
dc.subject.MESHPromoter Regions, Genetic-
dc.titleFunctional characterization of MATE2-K genetic variants and their effects on metformin pharmacokinetics-
dc.typeArticle-
dc.contributor.collegeOthers-
dc.contributor.departmentSeverance Hospital (세브란스병원)-
dc.contributor.googleauthorChung, Jae-Yong-
dc.contributor.googleauthorCho, Sung Kweon-
dc.contributor.googleauthorKim, Tae Hee-
dc.contributor.googleauthorKim, Kyoung Hee-
dc.contributor.googleauthorJang, Geun Hye-
dc.contributor.googleauthorKim, Choon Ok-
dc.contributor.googleauthorPark, Eun-Mi-
dc.contributor.googleauthorCho, Joo-Youn-
dc.contributor.googleauthorJang, In-Jin-
dc.contributor.googleauthorChoi, Ji Ha-
dc.identifier.doi10.1097/FPC.0b013e3283622037-
dc.contributor.localIdA04735-
dc.contributor.localIdA03829-
dc.relation.journalcodeJ02506-
dc.identifier.eissn1744-6880-
dc.identifier.pmid23652408-
dc.identifier.urlhttp://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&AN=01213011-201307000-00005&LSLINK=80&D=ovft-
dc.contributor.alternativeNameKim, Choon Ok-
dc.contributor.alternativeNameCho, Sung Kweon-
dc.contributor.affiliatedAuthor김춘옥-
dc.contributor.affiliatedAuthor조성권-
dc.citation.volume23-
dc.citation.number7-
dc.citation.startPage365-
dc.citation.endPage373-
dc.identifier.bibliographicCitationPHARMACOGENETICS AND GENOMICS, Vol.23(7) : 365-373, 2013-
dc.identifier.rimsid58584-
dc.type.rimsART-
Appears in Collections:
6. Others (기타) > Dept. of Clinical Pharmacology (임상시험센터) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers

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