Effect of ABCB1 diplotype on tacrolimus disposition in renal recipients depends on CYP3A5 and CYP3A4 genotype.
作者： T Vanhove , P Annaert , D Lambrechts , D R J Kuypers
DOI: 10.1038/TPJ.2016.49
关键词:
摘要: The relevance of most genetic polymorphisms beyond CYP3A5*1 on tacrolimus disposition remains unclear. We constructed a predictive mixed model for dose-corrected trough concentration (C0/dose) at months 3, 12 and 24 after transplantation in retrospective cohort 766 predominantly Causasian adult renal recipients (n=2042 concentrations). All patients were genotyped 32 single-nucleotide with proven or possible to based the previous studies. Of these, ABCB1, ABCC2, OATP1B1, COMT, FMO, PPARA APOA5 analyzed as (functional) diplotype groups. Predictors C0/dose CYP3A5*1, hematocrit, age, CYP3A4*22, use concomitant CYP3A4 inhibitor inducer, ALT, estimated glomerular filtration rate, formulation (once vs twice daily), ABCB1 time transplantation. effect was small but strongly accentuated CYP3A4*22 carriers non-existent CYP3A5 expressors. ABCC2 had limited that only statistically significant non-expressors.
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