title: Association of hemoglobin levels, CYP3A5, and NR1I3 gene polymorphisms with tacrolimus pharmacokinetics in liver transplant patients.
abstract: Tacrolimus is a widely used immunosuppressant after organ transplantation. The narrow therapeutic window and individual variability in tacrolimus pharmacokinetics make management of this agent a great challenge. This study was undertaken to determine the association of clinical markers, cytochrome P450, family 3, subfamily A, polypeptide 5 (CYP3A5) and nuclear receptor subfamily 1, group I, member 3 (NR1I3) gene polymorphisms with tacrolimus pharmacokinetics. A total of 96 liver transplant patients were enrolled in the study. Tacrolimus dose-adjusted trough concentration (C/D ratio) and clinical markers were recorded for one month after transplantation. CYP3A5 and NR1I3 gene polymorphisms for both donor and recipient were genotyped. In single variable analysis, hemoglobin (Hb), hematocrit (Hct), donor CYP3A5, NR1I3 gene polymorphisms and recipient CYP3A5 gene polymorphisms were associated with log-transformed tacrolimus C/D ratios. Hb, donor CYP3A5, NR1I3 gene polymorphisms and recipient CYP3A5 gene polymorphisms showed association with log-transformed tacrolimus C/D ratios in the final multiple linear regression model. Donor CYP3A5 polymorphisms were the most important variant, accounting for 14.3% of total variation involved in tacrolimus pharmacokinetics. This information could be useful in developing individualized tacrolimus treatment after liver transplantation.
authors.affiliation: Department of General Surgery, Shanghai First People's Hospital, School of Medicine, Shanghai Jiao Tong University.
authors.forename: Dawei
authors.initials: D
authors.lastname: Chen
authors.forename: Feng
authors.initials: F
authors.lastname: Guo
authors.forename: Jinxiu
authors.initials: J
authors.lastname: Shi
authors.forename: Chenhui
authors.initials: C
authors.lastname: Zhang
authors.forename: Zhaowen
authors.initials: Z
authors.lastname: Wang
authors.forename: Junwei
authors.initials: J
authors.lastname: Fan
authors.forename: Zhihai
authors.initials: Z
authors.lastname: Peng
mesh_terms: D000090702:Constitutive Androstane Receptor; D051544:Cytochrome P-450 CYP3A / Q000235:genetics*; D005260:Female; D005838:Genotype; D006454:Hemoglobins / Q000378:metabolism*; D006801:Humans; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics*; D016559:Tacrolimus / Q000493:pharmacokinetics*
chemical_list: D000090702:Constitutive Androstane Receptor; D006454:Hemoglobins; C000716327:NR1I3 protein, human; D018160:Receptors, Cytoplasmic and Nuclear; C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A; D016559:Tacrolimus