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(2) =0.30, P < 0.00005). The ABCB1 1199A carriers presented a 1.8-fold decreased cyclosporine intracellular concentration (P=0.04), whereas the 3435Tcarriers 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 > Tand 2677G > Tpolymorphisms 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. Pharmacogenetics and Genomics 18:307-315 (c) 2008 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.