Cited 26 times in
Functional characterization of MATE2-K genetic variants and their effects on metformin pharmacokinetics
DC Field | Value | Language |
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dc.contributor.author | 김춘옥 | - |
dc.contributor.author | 조성권 | - |
dc.date.accessioned | 2018-11-05T16:40:06Z | - |
dc.date.available | 2018-11-05T16:40:06Z | - |
dc.date.issued | 2013 | - |
dc.identifier.issn | 1744-6872 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/165025 | - |
dc.description.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. | - |
dc.description.statementOfResponsibility | restriction | - |
dc.language | English | - |
dc.publisher | Lippincott Williams & Wilkins | - |
dc.relation.isPartOf | PHARMACOGENETICS AND GENOMICS | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.rights | https://creativecommons.org/licenses/by-nc-nd/2.0/kr/ | - |
dc.subject.MESH | Asian Continental Ancestry Group | - |
dc.subject.MESH | Genetic Variation* | - |
dc.subject.MESH | Haplotypes | - |
dc.subject.MESH | Homozygote | - |
dc.subject.MESH | Humans | - |
dc.subject.MESH | Hypoglycemic Agents/pharmacokinetics* | - |
dc.subject.MESH | Metformin/pharmacokinetics* | - |
dc.subject.MESH | Organic Cation Transport Proteins/genetics* | - |
dc.subject.MESH | Polymorphism, Genetic | - |
dc.subject.MESH | Promoter Regions, Genetic | - |
dc.title | Functional characterization of MATE2-K genetic variants and their effects on metformin pharmacokinetics | - |
dc.type | Article | - |
dc.contributor.college | Others | - |
dc.contributor.department | Severance Hospital (세브란스병원) | - |
dc.contributor.googleauthor | Chung, Jae-Yong | - |
dc.contributor.googleauthor | Cho, Sung Kweon | - |
dc.contributor.googleauthor | Kim, Tae Hee | - |
dc.contributor.googleauthor | Kim, Kyoung Hee | - |
dc.contributor.googleauthor | Jang, Geun Hye | - |
dc.contributor.googleauthor | Kim, Choon Ok | - |
dc.contributor.googleauthor | Park, Eun-Mi | - |
dc.contributor.googleauthor | Cho, Joo-Youn | - |
dc.contributor.googleauthor | Jang, In-Jin | - |
dc.contributor.googleauthor | Choi, Ji Ha | - |
dc.identifier.doi | 10.1097/FPC.0b013e3283622037 | - |
dc.contributor.localId | A04735 | - |
dc.contributor.localId | A03829 | - |
dc.relation.journalcode | J02506 | - |
dc.identifier.eissn | 1744-6880 | - |
dc.identifier.pmid | 23652408 | - |
dc.identifier.url | http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&AN=01213011-201307000-00005&LSLINK=80&D=ovft | - |
dc.contributor.alternativeName | Kim, Choon Ok | - |
dc.contributor.alternativeName | Cho, Sung Kweon | - |
dc.contributor.affiliatedAuthor | 김춘옥 | - |
dc.contributor.affiliatedAuthor | 조성권 | - |
dc.citation.volume | 23 | - |
dc.citation.number | 7 | - |
dc.citation.startPage | 365 | - |
dc.citation.endPage | 373 | - |
dc.identifier.bibliographicCitation | PHARMACOGENETICS AND GENOMICS, Vol.23(7) : 365-373, 2013 | - |
dc.identifier.rimsid | 58584 | - |
dc.type.rims | ART | - |
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