A Pharmacogenomic Study on the Pharmacokinetics of Tacrolimus in Healthy Subjects Using the DMETTM Plus Platform
作者： Y Choi , F Jiang , H An , H J Park , J H Choi
DOI: 10.1038/TPJ.2015.99
关键词:
摘要: Genetic association studies on the pharmacokinetics of tacrolimus have reported conflicting results, except for role CYP3A5*3 polymorphism. The objective this study was to identify genetic variants affecting using DMETTM Plus microarray in 42 healthy males. Aside from CYP3A5*3, rs3814055 polymorphism NR1I2 gene associated with based false discovery rate-corrected multiple tests and least absolute shrinkage selection operator analysis. area under concentration-time curve last quantifiable time point (AUClast) 3.42 times greater subjects homozygous mutations both genes (CYP3A5*3/*3 T/T) than wild-type subjects. two explained 54% variability AUClast. An vitro luciferase reporter assay indicated that downregulation PXR expression is likely molecular mechanism responsible increased exposure carrying C>T variant.
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