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Background: Immunosuppressive therapy (IT) such as tacrolimus are influenced by pglycoprotein (P-gp) which modulates cellular efflux of this drug. P-gp is present on peripheral mononuclear cells (PBMC) and is encoded by the ABCB1 gene. No data are available regarding the impact of race on ABCB1 gene expression in PBMCs post-transplant over IT dosing interval. Methods: An observational study was completed in 20 African American (AA) and 11 Caucasian (C) stable renal transplant recipients (RTR) (ages 30-74 yrs) receiving tacrolimus (trough: 5 - 10 ng /ml), and enteric coated mycophenolate sodium. At time 0 (prior to IT) & 4, 8 and 12 hours after immunosuppression, PBMCs were collected for ABCB1 gene expression analysis by quantitative real-time-polymerase chain reaction (QRT-PCR). The target ABCB1 gene PCR product was cloned, and verified by sequencing. The cloned ABCB1 gene was used to establish standard curves (linear over 6 orders of magnitude; r 2=0.996) and assess PCR efficiencies. Total ABCB1 copies and normalized copies using Alien RNA were assessed. Results: The normalized (pABCB1 gene expression was higher among Caucasians and at each time until 12 hours. See Table below. Conclusions: The racial differences in ABCB1 gene expression was noted with greater expression in Caucasians than African Americans. These racial differences in ABCB1 gene expression may influence intracellular tacrolimus concentrations mediated by P-gp and affect clinical outcomes relative to African Americans and Caucasians
Pharmacy and Pharmaceutical Sciences
Brazeau, Daniel A.; Tornatore, Kathleen; Gundroo, Aijaz; and Venuto, Rocco, "Racial Influence on ABCB1 Gene Expression in Peripheral Blood Mononuclear Cells in Stable Renal Transplant Recipients" (2011). Pharmaceutical Sciences Faculty Posters. Poster 1.