Please use this identifier to cite or link to this item:
|Scopus||Web of Science®||Altmetric|
|Title:||CYP3A5*3 and ABCB1 61A>G significantly influence dose-adjusted trough blood tacrolimus concentrations in the first three months post-kidney transplantation|
|Citation:||Basic and Clinical Pharmacology and Toxicology, 2018; 123(3):320-326|
|Rong Hu, Daniel T. Barratt, Janet K. Coller, Benedetta C. Sallustio and Andrew A. Somogyi|
|Abstract:||Tacrolimus (TAC) is a first-line immunosuppressant used to prevent organ rejection after kidney transplantation. There is large inter-individual variability in its pharmacokinetics. Single nucleotide polymorphisms (SNPs) in genes encoding TAC metabolizing enzymes cytochromes P450 3A4/5 (CYP3A4/5), P-glycoprotein efflux transporter (ABCB1), their expression regulator pregnane X receptor (NR1I2) and CYP3A co-factor cytochrome P450 reductase (POR) have been studied for their effects on tacrolimus disposition. However, except for CYP3A5*3, controversies remain about their roles in predicting dose-adjusted trough blood TAC concentrations (C0 /D). This study aimed to investigate the effects of ABCB1 (61A>G, 1199G>A, 1236C>T, 2677G>T and 3435C>T), CYP3A4*22, CYP3A5*3, NR1I2 (8055C>T, 63396C>T and -25385C>T) and POR*28 SNPs on TAC C₀/D. In total, 165 kidney transplant recipients were included in this study. SNPs were genotyped by probe-based real-time polymerase chain reaction. Associations between log-transformed whole blood TAC C₀/D (measured at 1 and 3 months post-transplant) and genotypes/haplotypes were assessed by linear mixed effects analysis, controlling for age, sex and haematocrit. It was observed that CYP3A5 expressors (*1/*1 + *1/*3) (p = 5.5 × 10⁻¹⁶ ) and ABCB1 61G allele carriers (p = 0.001) had lower log-transformed TAC C₀/D (56% and 26% lower geometric mean TAC C₀/D, respectively) and accounted for approximately 30% and 4%, respectively, of log-transformed TAC C₀/D variability in the first 3 months post-transplant. In conclusion, CYP3A5*3 is a major, and ABCB1 61A>G is a novel, although minor, genetic factor affecting TAC C₀/D in kidney transplant recipients.|
|Keywords:||Humans; Tacrolimus; Immunosuppressive Agents; Kidney Transplantation; Retrospective Studies; Dose-Response Relationship, Drug; Genotype; Haplotypes; Polymorphism, Single Nucleotide; Alleles; Adolescent; Adult; Aged; Middle Aged; Female; Male; Cytochrome P-450 CYP3A; Young Adult; Real-Time Polymerase Chain Reaction; ATP Binding Cassette Transporter, Sub-Family B|
|Rights:||© 2018 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society)|
|Appears in Collections:||Pharmacology publications|
Files in This Item:
There are no files associated with this item.
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.