Do Drug Transporter (ABCB1) SNPs Influence Cyclosporine and Tacrolimus Dose Requirements and Renal Allograft Outcome in the Posttransplantation Period?

作者：Singh Ranjana; Srivastava Aneesh; Kapoor Rakesh; Mittal Rama Devi^*

来源：The Journal of Clinical Pharmacology, 2011, 51(4): 603-615.

DOI：10.1177/0091270010370704

• ABCB1
• allograft outcome
• cyclosporine A
• gene polymorphism
• renal transplantation
• tacrolimus

Polymorphisms in the drug transporter gene (ABCB1) may play a significant role in individualizing cyclosporine (CsA) and tacrolimus (Tac) dosage and subsequently the allograft outcome in renal transplant recipients. In total, 225 recipients on CsA and 75 on Tac-based immunosuppression regimen were recruited, and 6 common polymorphic sites in the ABCB1 gene were analyzed for association with dose-adjusted levels of CsA/Tac. Furthermore, association of ABCB1 single-nucleotide polymorphisms (SNPs) with allograft outcome was examined. GG and CC genotype patients at ABCB1 2677G > T and ABCB1 3435C > T were associated with lower dose-adjusted levels of CsA and Tac at 1 month (P = .057, P = .034), 3 months (P = .001, P = .015), and 6 months (P = .043) posttransplantation. Wild-type patients at 1236C > T (log P = .025) and 2677G > T (log P = .002) in CsA and 2677G > T (log P = .008) and 3435C > T (log P = .015) in Tac therapy patients demonstrated lower mean time to allograft rejection. No influence of ABCB1 haplotypes on CsA/Tac dose-adjusted levels was observed. Wild-type patients at ABCB1 2677G > T and 3435C > T were associated with lower dose-adjusted levels and thereby were at increased risk of allograft rejection because of under-immunosuppression in the early part of posttransplantation. Thus, genetic evaluation may be helpful to identify patients at risk for allograft rejection and also to individualize immunosuppressant dosing.

• 出版日期2011-4