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A pharmacogenomic study on the pharmacokinetics of tacrolimus in healthy subjects using the DMET™ Plus platform
DMET™ Plus genotyping platform을 이용한 Tacrolimus의 약물유전체 연구

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Authors
최윤정
Advisor
정재용
Major
의과대학 협동과정임상약리학전공
Issue Date
2016
Publisher
서울대학교 대학원
Keywords
TacrolimusPharmacogenomicsPharmacokineticsFDRLASSO
Description
학위논문 (석사)-- 서울대학교 대학원 : 협동과정 임상약리학 전공, 2016. 2. 정재용.
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
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.
Language
English
URI
http://hdl.handle.net/10371/132327
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College of Medicine/School of Medicine (의과대학/대학원)Program in Clinical Pharmacology (협동과정-임상약리학전공)Theses (Master's Degree_협동과정-임상약리학전공)
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