Associations of ABCB1 3435C>T and IL-10-1082G>A polymorphisms with long-term sirolimus dose requirements in renal transplant patients.
Associations of ABCB1 3435C>T and IL-10-1082G>A polymorphisms with long-term sirolimus dose requirements in renal transplant patients.
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DOI：
10.1097/tp.0b013e3182384ae2
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发表时间：
2011-12-27
期刊：
影响因子：
6.2
通讯作者：
Hon YY
中科院分区：
文献类型：
--
作者：
Sam WJ;Chamberlain CE;Lee SJ;Goldstein JA;Hale DA;Mannon RB;Kirk AD;Hon YY
SRL absorption and metabolism are affected by Pgp-mediated transport and CYP3A enzyme activity, which are further under the influences of cytokine concentrations. This retrospective study determined the associations of ABCB1 1236C>T, 2677 G>T/A, and 3435C>T, CYP3A4 -392A>G, CYP3A5 6986A>G and 14690G>A, IL-10 -1082G>A, and 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 post initiation of SRL. 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 post transplantation were analyzed using a linear mixed-effects model, with adjustments for body mass index and weight-normalized doses of tacrolimus, prednisone, clotrimazole, and statins. 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 to -1082AG/AA. 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.
