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dc.contributor.author박은미*
dc.contributor.author최지하*
dc.date.accessioned2016-08-28T11:08:14Z-
dc.date.available2016-08-28T11:08:14Z-
dc.date.issued2013*
dc.identifier.issn1744-6872*
dc.identifier.otherOAK-10758*
dc.identifier.urihttps://dspace.ewha.ac.kr/handle/2015.oak/227281-
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 ofMATE2-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. © Lippincott Williams & Wilkins.*
dc.languageEnglish*
dc.titleFunctional characterization of MATE2-K genetic variants and their effects on metformin pharmacokinetics*
dc.typeArticle*
dc.relation.issue7*
dc.relation.volume23*
dc.relation.indexSCI*
dc.relation.indexSCIE*
dc.relation.indexSCOPUS*
dc.relation.startpage365*
dc.relation.lastpage373*
dc.relation.journaltitlePharmacogenetics and Genomics*
dc.identifier.doi10.1097/FPC.0b013e3283622037*
dc.identifier.wosidWOS:000327694900005*
dc.identifier.scopusid2-s2.0-84879128112*
dc.author.googleChung J.Y.*
dc.author.googleCho S.K.*
dc.author.googleKim T.H.*
dc.author.googleKim K.H.*
dc.author.googleJang G.H.*
dc.author.googleKim C.O.*
dc.author.googlePark E.M.*
dc.author.googleCho J.Y.*
dc.author.googleJang I.J.*
dc.author.googleChoi J.H.*
dc.contributor.scopusid박은미(35933416400)*
dc.contributor.scopusid최지하(35080057300)*
dc.date.modifydate20240123095000*
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의과대학 > 의학과 > Journal papers
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