Publications
Detailed Information
A pharmacogenomic study on the pharmacokinetics of tacrolimus in healthy subjects using the DMET™ Plus platform : DMET™ Plus genotyping platform을 이용한 Tacrolimus의 약물유전체 연구
DC Field | Value | Language |
---|---|---|
dc.contributor.advisor | 정재용 | - |
dc.contributor.author | 최윤정 | - |
dc.date.accessioned | 2017-07-19T10:08:37Z | - |
dc.date.available | 2017-07-19T10:08:37Z | - |
dc.date.issued | 2016-02 | - |
dc.identifier.other | 000000133522 | - |
dc.identifier.uri | https://hdl.handle.net/10371/132327 | - |
dc.description | 학위논문 (석사)-- 서울대학교 대학원 : 협동과정 임상약리학 전공, 2016. 2. 정재용. | - |
dc.description.abstract | Genetic association studies on the pharmacokinetics of tacrolimus have reported conflicting results, except for the role of the CYP3A5*3 polymorphism. The objective of this study was to identify genetic variants affecting the pharmacokinetics of tacrolimus using the DMET™ Plus microarray in 42 healthy males. Aside from CYP3A5*3, the rs3814055 polymorphism in the NR1I2 gene was associated with the tacrolimus pharmacokinetics based on false discovery rate-corrected multiple tests and the least absolute shrinkage and selection operator analysis. The area under the concentration-time curve to the last quantifiable time-point (AUClast) was 3.42 times greater in subjects with homozygous mutations in both genes (CYP3A5*3/*3 and NR1I2 T/T) than in wild-type subjects. The two variants explained the 54% variability in the tacrolimus AUClast.
Our results agree with previous studies that CYP3A5*3 (rs776746) has a significant impact on the tacrolimus PK. The association identified for the first time between a SNP (rs3814055) in NR1I2 gene and the tacrolimus PK is interesting because NR1I2 gene encodes PXR, a transcriptional regulator of CYP3A enzymes | - |
dc.description.abstract | however, this association warrants further in-vitro and in-vivo studies. Using more than just one data analysis method may improve the interpretation of the results of gene association studies. | - |
dc.description.tableofcontents | INTRODUCTION 1
SUBJECT AND METHODS 4 Clinical study 4 Determination of plasma concentrations of tacrolimus 6 Pharmacokinetic analysis 6 Genotyping analysis 7 Statistical analysis 8 RESULTS 10 Subjects 10 Genetic associations with tacrolimus pharmacokinetics 11 Genetic effects of CYP3A5 and NR1I2 on tacrolimus pharmacokinetics 16 DISCUSSION 21 REFERENCES 27 Abstract in Korean 31 | - |
dc.format | application/pdf | - |
dc.format.extent | 2048387 bytes | - |
dc.format.medium | application/pdf | - |
dc.language.iso | en | - |
dc.publisher | 서울대학교 대학원 | - |
dc.subject | Tacrolimus | - |
dc.subject | Pharmacogenomics | - |
dc.subject | Pharmacokinetics | - |
dc.subject | FDR | - |
dc.subject | LASSO | - |
dc.subject.ddc | 615 | - |
dc.title | A pharmacogenomic study on the pharmacokinetics of tacrolimus in healthy subjects using the DMET™ Plus platform | - |
dc.title.alternative | DMET™ Plus genotyping platform을 이용한 Tacrolimus의 약물유전체 연구 | - |
dc.type | Thesis | - |
dc.description.degree | Master | - |
dc.citation.pages | 33 | - |
dc.contributor.affiliation | 의과대학 협동과정임상약리학전공 | - |
dc.date.awarded | 2016-02 | - |
- Appears in Collections:
- Files in This Item:
Item View & Download Count
Items in S-Space are protected by copyright, with all rights reserved, unless otherwise indicated.