Influence of ABCB1 genetic polymorphisms on cyclosporine intracellular concentration in transplant recipients.
OBJECTIVE
The expression on lymphocytes of P-glycoprotein, an efflux transporter encoded by the ABCB1 gene, might influence cyclosporine intracellular concentration.


METHODS
ABCB1 genotypes, cyclosporine intracellular and blood concentrations were determined in 64 stable renal, liver or lung transplant recipients.


RESULTS
Cyclosporine intracellular concentration correlated moderately with blood concentration (r=0.30, P<0.00005). The ABCB1 1199A carriers presented a 1.8-fold decreased cyclosporine intracellular concentration (P=0.04), whereas the 3435T carriers presented a 1.7-fold increase (P=0.02) as well as a 1.2-fold increased blood concentration (P=0.04). In contrast, ABCB1 61A>G, 1236C>T and 2677G>T polymorphisms did not influence cyclosporine intracellular and blood concentrations.


CONCLUSIONS
This is the first report demonstrating that ABCB1 polymorphisms influence cyclosporine intracellular concentration. Interestingly, its influence on intracellular concentration is significantly higher than on blood concentration (P<0.002). This may therefore modulate cyclosporine immunosuppressive activity.
Crettol
Séverine
S
Unit of Biochemistry and Clinical Psychopharmacology, Centre of Psychiatric Neuroscience, Department of Psychiatry, CHUV, University of Lausanne, Hospital of Cery, Prilly, Switzerland.
Venetz
Jean-Pierre
JP
Fontana
Massimiliano
M
Aubert
John-David
JD
Ansermot
Nicolas
N
Fathi
Marc
M
Pascual
Manuel
M
Eap
Chin B
CB
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000328:Adult; D000368:Aged; D016572:Cyclosporine / Q000008:administration & dosage / Q000378:metabolism*; D005260:Female; D005838:Genotype; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000378:metabolism*; D016030:Kidney Transplantation; D016031:Liver Transplantation; D016040:Lung Transplantation; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D007166:Immunosuppressive Agents; D012333:RNA, Messenger; D016572:Cyclosporine