Long-term effects of ABCB1 and SXR SNPs on the systemic exposure to cyclosporine in pediatric kidney transplant patients

FerraressoM.; BelingheriM.; TuroloS.; GhioL.; TirelliA.S.; GrilloP.; LeporeM.; EdefontiA.

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Long-term effects of ABCB1 and SXR SNPs on the systemic exposure to cyclosporine in pediatric kidney transplant patients

机译：ABCB1和SXR SNPs对小儿肾脏移植患者全身暴露于环孢素的长期影响

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Aim: Cyclosporine is characterized by a wide interindividual variability in its pharmacokinetics. The objective of this study was to evaluate the effects of ABCB1 and SXR SNPs on cyclosporine exposure in a group of kidney transplant patients followed up from childhood to adulthood. Patients & methods: Recipients were genotyped for ABCB1 C1236T, G2677T/A and C3435T, and for SXR RS3842689 and A7635G. Dose-adjusted trough levels and weight-adjusted daily doses were compared among patients according to allelic status by a generalized estimation equation approach that allows longitudinal data analyses. Results: A genotype-dependent effect was found in all ABCB1 genotypes and in one of the SXR SNPs. This effect was particularly evident for the TT genotype of the ABCB1 G2677T/A SNP, the TT genotype of the ABCB1 C3435T SNP and for heterozygotes of the deletion of 6 bp in the promoter region of SXR. Conclusion: The presence of specific ABCB1 and SXR SNPs could significantly affect cyclosporine exposure during a kidney transplant patients development from childhood to adulthood in a time-dependent fashion. Original submitted 3 May 2013; Revision submitted 25 July 201.

机译：目的：环孢霉素的药代动力学特征是个体差异很大。这项研究的目的是评估ABCB1和SXR SNP对一组从儿童期到成年的肾脏移植患者环孢素暴露的影响。患者与方法：对ABCB1 C1236T，G2677T / A和C3435T以及SXR RS3842689和A7635G的收件人进行基因分型。根据等位基因状态，通过允许纵向数据分析的广义估计方程方法，比较了患者之间的剂量调整谷值水平和体重调整后的日剂量。结果：在所有ABCB1基因型和一种SXR SNP中均发现了基因型依赖性效应。对于ABCB1 G2677T / A SNP的TT基因型，ABCB1 C3435T SNP的TT基因型以及SXR启动子区域中6 bp缺失的杂合子，这种效果尤为明显。结论：特定的ABCB1和SXR SNP的存在可以显着影响肾脏移植患者从儿童期到成年期的环孢素暴露，并呈时间依赖性。原件于2013年5月3日提交;修订于201年7月25日提交。

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《Pharmacogenomics》 |2013年第13期|共9页
作者
FerraressoM.; BelingheriM.; TuroloS.; GhioL.; TirelliA.S.; GrilloP.; LeporeM.; EdefontiA.;
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正文语种 eng
中图分类药学;
关键词
ABCB1; cyclosporine; developmental pharmacology; pediatric kidney transplantation; pharmacogenetic; pharmacokinetic; single nucleotide polymorphism; SXR;

机译：ABCB1;环孢素;发育药理学;小儿肾脏移植;药物遗传学;药代动力学;单核苷酸多态性;SXR;

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1. Long-term effects of ABCB1 and SXR SNPs on the systemic exposure to cyclosporine in pediatric kidney transplant patients [J] . FerraressoM., BelingheriM., TuroloS., Pharmacogenomics . 2013,第13期

机译：ABCB1和SXR SNPs对小儿肾脏移植患者全身暴露于环孢素的长期影响
2. Weight of ABCB1 and POR genes on oral tacrolimus exposure in CYP3A5 nonexpressor pediatric patients with stable kidney transplant. [J] . G N Almeida-Paulo, I Dapía García, R Lubomirov, The pharmacogenomics journal . 2018,第1期

机译：ABCB1和POR基因的重量在CYP3A5中口腔肾脏移植口口腔Tacrolimus暴露中的重量。
3. Investigation of CYP 3A5 and ABCB1 gene polymorphisms in the long-term following renal transplantation: Effects on tacrolimus exposure and kidney function [J] . Stefanovic Nikola Z., Cvetkovic Tatjana P., Jevtovic-Stoimenov Tatjana M., Experimental and therapeutic medicine . 2015,第3期

机译：CYP 3A5和ABCB1基因多态性在肾脏移植后的长期研究：对他克莫司暴露和肾脏功能的影响
4. Prediction of Cyclosporine Blood Concentration and Dosage in Kidney Transplantation Patients: Comparison of Multiple Linear Regression and Neural Networks [C] . Shan Li, Yao Chen, Qin Yan ICCEE 2010;International conference on computer and electrical engineering . 2010

机译：肾移植患者环孢素血药浓度和剂量的预测：多重线性回归和神经网络的比较
5. The long-term effectiveness of dialysis, kidney transplantation and pancreas transplantation for patients with diabetes mellitus and renal failure: A decision analysis. [D] . Knoll, Gregory Allan. 2002

机译：透析，肾脏移植和胰腺移植对糖尿病和肾衰竭患者的长期疗效：一项决策分析。
6. Investigation of CYP 3A5 and ABCB1 gene polymorphisms in the long-term following renal transplantation: Effects on tacrolimus exposure and kidney function [O] . NIKOLA Z. STEFANOVIĆ, TATJANA P. CVETKOVIĆ, TATJANA M. JEVTOVIĆ-STOIMENOV, -1

机译：CYP 3A5和ABCB1基因多态性在肾脏移植后的长期研究：对他克莫司暴露和肾脏功能的影响
7. Do drug transporter (ABCB1) SNPs and P-glycoprotein function influence cyclosporine and macrolides exposure in renal transplant patients? Results of the pharmacogenomic substudy within the symphony study [O] . Llaudo Ines, Colom Helena, Gimenez-Bonafe Pepita, 2013

机译：药物转运蛋白（aBCB1）sNps和p-糖蛋白功能是否会影响肾移植患者的环孢菌素和大环内酯类药物的暴露？交响乐研究中药物基因组亚研究的结果

Long-term effects of ABCB1 and SXR SNPs on the systemic exposure to cyclosporine in pediatric kidney transplant patients

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