Cited 11 times in
Association of a synonymous GAT3 polymorphism with antiepileptic drug pharmacoresistance
DC Field | Value | Language |
---|---|---|
dc.contributor.author | 김원주 | - |
dc.contributor.author | 이민구 | - |
dc.date.accessioned | 2014-12-20T17:47:08Z | - |
dc.date.available | 2014-12-20T17:47:08Z | - |
dc.date.issued | 2011 | - |
dc.identifier.issn | 1434-5161 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/95246 | - |
dc.description.abstract | It would be likely that the genetic variants of the GTA3 gene encoding GAT-3, an astrocytic GABA transporter, may alter gamma-aminobutyric acid (GABA) neurotransmission in the synaptic cleft in the epileptic brain and cause antiepileptic drugs (AEDs) pharmacoresistance. A candidate gene association analysis with fine mapping was performed to dissect the genetic contributions of GAT3 to AEDs pharmacoresistance. Two independent case sample sets were recruited (Samples 1 and 2), and each set was divided into two groups (drug-resistant and drug-responsive) according to the treatment outcomes with AEDs. Sample1 (n=400) was used for the initial exploratory stage of the study and sample 2 (n=435) was used for confirmation of the genetic association in the replication stage of the study. A GAT3 polymorphism (GAT3 c.1572 C>T, rs2272400) was nominally associated with AEDs pharmacoresistance (P(CC) vs P(CT/TT)=0.012, P(allelic)=0.01). The odds ratio (OR) for AED pharmacoresistance was 1.6 (95% confidence interval (CI), 1.11-2.24; P=0.01) in the additive models of inheritance. The statistical significance remained after we adjusted for a confounding factor, the etiology of epilepsy, at 0.012 (adjusted OR: 1.73, 95% CI: 1.13-2.67) and used Bonferroni's correction for multiple comparisons at 0.048. Importantly, the positive association of c.1572 T was reproduced in the replication stage (P(allelic)=0.037, joint P-value of the replication=0.001). The results suggest that GAT3 c.1572T may be one of the contributing factors with a modest effect on AEDs pharmacoresistance in the epileptic brain, shed light on a better understanding of the underlying mechanisms and serve as an impetus for new avenues of treatment for AEDs pharmacoresistance. | - |
dc.description.statementOfResponsibility | open | - |
dc.format.extent | 640~646 | - |
dc.relation.isPartOf | JOURNAL OF HUMAN GENETICS | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/2.0/kr/ | - |
dc.subject.MESH | Adolescent | - |
dc.subject.MESH | Adult | - |
dc.subject.MESH | Anticonvulsants/pharmacology* | - |
dc.subject.MESH | Anticonvulsants/therapeutic use | - |
dc.subject.MESH | Brain/drug effects | - |
dc.subject.MESH | Brain/metabolism | - |
dc.subject.MESH | Case-Control Studies | - |
dc.subject.MESH | Child | - |
dc.subject.MESH | Child, Preschool | - |
dc.subject.MESH | Drug Resistance/genetics* | - |
dc.subject.MESH | Epilepsy/drug therapy | - |
dc.subject.MESH | Epilepsy/etiology | - |
dc.subject.MESH | Epilepsy/genetics* | - |
dc.subject.MESH | Female | - |
dc.subject.MESH | GABA Plasma Membrane Transport Proteins/genetics* | - |
dc.subject.MESH | Genetic Predisposition to Disease* | - |
dc.subject.MESH | Genotype | - |
dc.subject.MESH | Haplotypes | - |
dc.subject.MESH | Humans | - |
dc.subject.MESH | Infant | - |
dc.subject.MESH | Male | - |
dc.subject.MESH | Polymorphism, Single Nucleotide/genetics* | - |
dc.subject.MESH | Republic of Korea | - |
dc.subject.MESH | Young Adult | - |
dc.subject.MESH | gamma-Aminobutyric Acid/metabolism | - |
dc.title | Association of a synonymous GAT3 polymorphism with antiepileptic drug pharmacoresistance | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.department | Dept. of Neurology (신경과학) | - |
dc.contributor.googleauthor | Dong-Uk Kim | - |
dc.contributor.googleauthor | Myeong-Kyu Kim | - |
dc.contributor.googleauthor | Yong-Won Cho | - |
dc.contributor.googleauthor | Yo-Sik Kim | - |
dc.contributor.googleauthor | Won-Joo Kim | - |
dc.contributor.googleauthor | Min Goo Lee | - |
dc.contributor.googleauthor | Sung Eun Kim | - |
dc.contributor.googleauthor | Tai-Seung Nam | - |
dc.contributor.googleauthor | Ki-Hyun Cho | - |
dc.contributor.googleauthor | Young-Ok Kim | - |
dc.contributor.googleauthor | Min-Cheol Lee | - |
dc.identifier.doi | 10.1038/jhg.2011.73 | - |
dc.admin.author | false | - |
dc.admin.mapping | false | - |
dc.contributor.localId | A00771 | - |
dc.contributor.localId | A02781 | - |
dc.relation.journalcode | J01446 | - |
dc.identifier.eissn | 1435-232X | - |
dc.identifier.pmid | 21776001 | - |
dc.identifier.url | http://www.nature.com/jhg/journal/v56/n9/full/jhg201173a.html | - |
dc.contributor.alternativeName | Kim, Won Joo | - |
dc.contributor.alternativeName | Lee, Min Goo | - |
dc.contributor.affiliatedAuthor | Kim, Won Joo | - |
dc.contributor.affiliatedAuthor | Lee, Min Goo | - |
dc.rights.accessRights | not free | - |
dc.citation.volume | 56 | - |
dc.citation.number | 9 | - |
dc.citation.startPage | 640 | - |
dc.citation.endPage | 646 | - |
dc.identifier.bibliographicCitation | JOURNAL OF HUMAN GENETICS, Vol.56(9) : 640-646, 2011 | - |
dc.identifier.rimsid | 28204 | - |
dc.type.rims | ART | - |
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