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• W2048839618 abstract "Backgrounds. Sirolimus (SRL) absorption and metabolism are affected by p-glycoprotein-mediated transport and CYP3A enzyme activity, which are further under the influences of cytokine concentrations. This retrospective study determined the associations of adenosine triphosphate-binding cassette, subfamily B, member 1 (ABCB1) 1236C>T, 2677 G>T/A, and 3435C>T, cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) −392A>G, cytochrome P450, family 3, subfamily A, polypeptide 5 (CYP3A5) 6986A>G and 14690G>A, interleukin (IL)-10 −1082G>A, and tumor necrosis factor (TNF) −308G>A polymorphisms with SRL dose-adjusted, weight-normalized trough concentrations (C/D) at 7 days, and at 1, 3, 6, and 12 months after initiation of SRL. Methods. Genotypes for 86 renal transplant patients who received SRL-based maintenance immunosuppressive therapy were determined using polymerase chain reaction followed by chip-based mass spectrometry. The changes of log-transformed C/D over the days posttransplantation were analyzed using a linear mixed-effects model, with adjustments for body mass index and weight-normalized doses of tacrolimus, prednisone, clotrimazole, and statins. Results. ABCB1 3435C>T and IL-10 −1082G>A were significantly associated with log C/D (P=0.0016 and 0.0394, respectively). Mean SRL C/D was 48% higher in patients with ABCB1 3435CT/TT genotype than those with 3435CC genotype, and was 24% higher in IL-10 −1082GG compared with −1082AG/AA. Conclusions. ABCB1 3435C>T and IL-10 −1082G>A were significantly associated with long-term SRL dose requirements. Genetics can play a significant role in SRL dosing and may be useful in therapeutic monitoring of SRL in renal transplantation. Future replication studies are needed to confirm these associations." @default.
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• W2048839618 date "2011-12-27" @default.
• W2048839618 modified "2023-10-16" @default.
• W2048839618 title "Associations of ABCB1 3435C>T and IL-10-1082G>A Polymorphisms With Long-Term Sirolimus Dose Requirements in Renal Transplant Patients" @default.
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• W2048839618 doi "https://doi.org/10.1097/tp.0b013e3182384ae2" @default.
• W2048839618 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3237821" @default.
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