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


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.


CONCLUSIONS
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.
Capron
Arnaud
A
Department of Clinical Chemistry, Cliniques universitaires St Luc, Université Catholique de Louvain, Brussels, Belgium.
Mourad
Michel
M
De Meyer
Martine
M
De Pauw
Luc
L
Eddour
Djamila Chaib
DC
Latinne
Dominique
D
Elens
Laure
L
Haufroid
Vincent
V
Wallemacq
Pierre
P
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics; D000328:Adult; D001773:Blood Cells; D019411:Clinical Laboratory Techniques; D051544:Cytochrome P-450 CYP3A; D005091:Exons; D005260:Female; D005838:Genotype; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007438:Introns; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D012106:Research; D016559:Tacrolimus / Q000627:therapeutic use
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D007166:Immunosuppressive Agents; C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A; D016559:Tacrolimus