Session Time: 4:00pm-5:30pm
Presentation Time: 5:00pm-5:12pm
Location: Terrace IV
Purpose: African Americans (AA) renal transplant recipients (RTR) have poorer long term allograft survival compared to Caucasians(C) which may be attributed to racial differences in calcineurin inhibitor pharmacology. P-glycoprotein (P-gp), an ABC transporter expressed in liver, gut, kidney and peripheral blood mononuclear cells (PBMCs), modulates tacrolimus (TAC) pharmacokinetics and intracellular pharmacology impacting overall patient response. ABCB1 encodes for P-gp with a primary variant (TTT) associated with altered function compared to wild-type (CGC). This study evaluated P-gp function in PBMCs in AA and C males(M) and females(F) at troughs and 4 hours after TAC with ABCB1 haplotypes in RTR.
Methods: P-gp function in PBMC was quantitated in 67 stable RTR receiving tacrolimus (trough: 7.2 ± 1.9 ng/ml) and mycophenolic acid immunosuppression for ≥ 6 months. The P-gp function was quantified by flow cytometric measurement of cyclosporine (CYA, 2.5 ¯o;M) -reversible efflux of the P-gp substrate, DiOC2(3) by % change of Mean Fluorescent Intensity (MFI) with CYA (% δMFI-CYA) at TAC trough (0 hours) and 4 hours(peak). A 50% increase in %δMFI-CYA correlates with significant P-gp function based on P-gp-expressing cell line models. ABCB1 single nucleotide polymorphisms: c.1236C>T (rs1128503), c.2677G>T (rs2032582), and c.3435C>T (rs1045642) were determined and haplotype associations estimated by THESIAS.
Results: P-gp function are summarized in table by race and sex. A significant race effect was found. The patients with variant TTT had 29% increased P-gp function (p=0.057) at the TAC peak with no race or gender effects.
|Time (hrs)||AAM (n=22)||AAF (n=13)||CM (n=16)||CF (n=16)||P Value|
|4||83.6(46.8)||52.2(32.7)||83.8 (39.3)||108.4(87.0)||Race x Sex:0.104|
CONCLUSION: P-gp function in PBMC demonstrated race effects with reduced function in AA RTR. Measurement of P-glycoprotein function in PBMC may provide insight into interpatient variability in intracellular tacrolimus pharmacology.
To cite this abstract in AMA style:Tornatore K, Minderman H, O'Loughlin K, Attwood K, Brazeau D, Venuto R. Influence of Race on P-Glycoprotein Function in Peripheral Blood Mononuclear Cells [abstract]. Am J Transplant. 2015; 15 (suppl 3). https://atcmeetingabstracts.com/abstract/influence-of-race-on-p-glycoprotein-function-in-peripheral-blood-mononuclear-cells/. Accessed February 22, 2020.
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