A pharmacogenomic study on the pharmacokinetics of tacrolimus in healthy subjects using the DMET TM Plus platform
- 등재 SCIE, SCOPUS
- 발행기관 Nature Publishing Group
- 발행년도 2017
- URI http://www.dcollection.net/handler/ewha/000000156366
- 본문언어 영어
- Published As http://dx.doi.org/10.1038/tpj.2015.99
초록/요약
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 TM 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 (AUC last) 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 AUC last. An in vitro luciferase reporter assay indicated that downregulation of PXR expression is the likely molecular mechanism responsible for the increased exposure to tacrolimus in subjects carrying the rs3814055 C>T variant. © 2017 The Author(s).
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