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Do Drug Transporter ( ABCB1 ) SNPs Influence Cyclosporine and Tacrolimus Dose Requirements and Renal Allograft Outcome in the Posttransplantation Period?
Author(s) -
Singh Ranjana,
Srivastava Aneesh,
Kapoor Rakesh,
Mittal Rama Devi
Publication year - 2011
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270010370704
Subject(s) - tacrolimus , immunosuppression , medicine , gastroenterology , transplantation , single nucleotide polymorphism , immunosuppressive drug , pharmacology , genotype , immunology , biology , gene , biochemistry
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.