CYP3A5 and ABCB1 polymorphisms influence tacrolimus concentrations in peripheral blood mononuclear cells after renal transplantation

被引：42

作者：

Capron, Arnaud ^{[1
,2
]}

Mourad, Michel ^{[3
]}

De Meyer, Martine ^{[3
]}

De Pauw, Luc ^{[3
]}

Eddour, Djamila Chaib ^{[3
]}

Latinne, Dominique ^{[4
]}

Elens, Laure ^{[2
]}

Haufroid, Vincent ^{[1
,2
]}

Wallemacq, Pierre ^{[1
,2
]}

机构：

[1] Catholic Univ Louvain, Dept Clin Chem, Lab Toxicol & Therapeut Drug Monitoring, Clin Univ St Luc, B-1200 Brussels, Belgium

[2] Catholic Univ Louvain, Louvain Ctr Toxicol & Appl Pharmacol, Clin Univ St Luc, B-1200 Brussels, Belgium

[3] Catholic Univ Louvain, Abdominal Transplantat Unit, Clin Univ St Luc, B-1200 Brussels, Belgium

[4] Catholic Univ Louvain, Immuno Haematol Dept, Clin Univ St Luc, B-1200 Brussels, Belgium

来源：

PHARMACOGENOMICS | 2010年 / 11卷 / 05期

关键词：

ABCB1; CYP3A5; peripheral blood mononuclear cell; pharmacogenetics; polymorphism; tacrolimus; transplantation; EFFLUX TRANSPORT ACTIVITY; MASS SPECTROMETRIC ASSAY; EARLY CELLULAR REJECTION; MDR1 GENE POLYMORPHISMS; P-GLYCOPROTEIN; LIVER-TRANSPLANTATION; CALCINEURIN INHIBITORS; ORGAN-TRANSPLANTATION; DOSE REQUIREMENTS; HEPATIC TISSUE;

D O I：

10.2217/PGS.10.43

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Aims: This prospective study investigated the effect of genetic polymorphisms in a biotransformation enzyme (CYP3A5) and a transporter protein (ABCB1) on tacrolimus (Tac) whole blood concentrations in renal transplantation, and more specifically on peripheral blood mononuclear cell (PBMC) drug concentrations, after renal transplantation. Materials & methods: A total of 96 renal transplant recipients were genotyped for the exon 11 (1199G>A), 21 (3435C>T) and 26 (2677G>T/A) polymorphisms in the ABCB1 gene and for the intron 3 polymorphism in the CYP3A5 gene. Tac blood and PBMC concentrations were determined at day 7 after transplantation and at steady state, and then compared with recipient genotypes. Results & conclusion: The ABCB1 1199G>A, 3435C>T and 2677G>T/A SNPs, appeared to reduce the activity of P-glycoprotein towards Tac, increasing Tac PBMC concentrations. The impact of ABCB1 genetic polymorphisms on Tac blood concentrations was negligible. As increased Tac intracellular concentrations might in turn enhance immunosuppressive status and prevention or rejection, ABCB1 recipient genotyping might be useful to better individualize the Tac immunosuppressive therapy in renal transplantation.

引用

页码：703 / 714

页数：12

共 45 条

[1] Association of the multidrug resistance-1 gene single-nucleotide polymorphisms with the tacrolimus dose requirements in renal transplant recipients [J].