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Influence of ABCB1 genetic polymorphisms on cyclosporine intracellular concentration in transplant recipients.

Crettol S, Venetz JP, Fontana M, Aubert JD, Ansermot N, Fathi M, Pascual M, Eap CB

Unit of Biochemistry and Clinical Psychopharmacology, Centre of Psychiatric Neuroscience, Department of Psychiatry, CHUV, University of Lausanne, Hospital of Cery, Prilly, Switzerland.

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. CONCLUSION: 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.

Published 12 March 2008 in Pharmacogenet Genomics, 18(4): 307-15.
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