Impact of the CYP3A5, CYP3A4, COMT, IL-10 and POR genetic polymorphisms on tacrolimus metabolism in Chinese renal transplant recipients.
Impact of the CYP3A5, CYP3A4, COMT, IL-10 and POR genetic polymorphisms on tacrolimus metabolism in Chinese renal transplant recipients.
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DOI：
10.1371/journal.pone.0086206
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Zhou L
中科院分区：
文献类型：
--
作者：
Li CJ;Li L;Lin L;Jiang HX;Zhong ZY;Li WM;Zhang YJ;Zheng P;Tan XH;Zhou L
他克莫司是一种广泛使用的免疫抑制药物，用于预防实体器官移植的排斥反应。他克莫司的疗效表现出相当大的变异性，这可能与受者之间的遗传差异有关。我们对240例接受他克莫司免疫抑制治疗的中国肾移植受者进行了回顾性研究。所有患者均于移植后40d内进行回顾性资料收集。通过抓拍方法检测到17个单核苷酸多态，分别位于细胞色素P3A5、细胞色素P3A4、COMT、IL-10和POR。他克莫司的血药浓度在移植后第1-3天、第6-8天和第12-14天，以及在预定的治疗浓度范围内获得。用Kruskal-Wallis检验检测遗传变异对不同时间点他克莫司浓度/剂量比(C0/D)的影响。用卡方检验比较移植后1、2、3、4周不同基因型组患者达到目标C0范围的比例。经多项检测校正后，移植后不同时间点C0/D与细胞色素P3A5*3、细胞色素P3A4*1G和细胞色素P3A4rs4646437T>；C显著相关。在移植后3周，IL-10rs1800871-TT组达到目标C0范围的患者比例高于IL-10rs1800871-CT和IL-10rs1800871-CC组(p = 0.004)。CYP3A5*3、CYP3A4*1G、CYP3A4 rs46437 T>；C和IL-10 rs1800871 C>；T可能是影响中国肾移植受者他克莫司代谢个体间变异的潜在多态。
Tacrolimus is a widely used immunosuppressive drug for preventing the rejection of solid organ transplants. The efficacy of tacrolimus shows considerable variability, which might be related to genetic variation among recipients. We conducted a retrospective study of 240 Chinese renal transplant recipients receiving tacrolimus as immunosuppressive drug. The retrospective data of all patients were collected for 40 days after transplantation. Seventeen SNPs of CYP3A5, CYP3A4, COMT, IL-10 and POR were identified by the SNaPshot assay. Tacrolimus blood concentrations were obtained on days 1–3, days 6–8 and days 12–14 after transplantation, as well as during the period of the predefined therapeutic concentration range. Kruskal–Wallis test was used to examine the effect of genetic variation on the tacrolimus concentration/dose ratio (C 0/D) at different time points. Chi-square test was used to compare the proportions of patients who achieved the target C 0 range in the different genotypic groups at weeks 1, 2, 3 and 4 after transplantation. After correction for multiple testing, there was a significant association of C 0/D with CYP3A5*3, CYP3A4*1G and CYP3A4 rs4646437 T>C at different time points after transplantation. The proportion of patients in the IL-10 rs1800871-TT group who achieved the target C 0 range was greater (p = 0.004) compared to the IL-10 rs1800871-CT and IL-10 rs1800871-CC groups at week 3 after transplantation. CYP3A5*3, CYP3A4 *1G, CYP3A4 rs4646437 T>C and IL-10 rs1800871 C>T might be potential polymorphisms affecting the interindividual variability in tacrolimus metabolism among Chinese renal transplant recipients.
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DOI：
10.1038/tpj.2010.28
发表时间：
2011-08
期刊：
The pharmacogenomics journal
影响因子：
--
作者：
Wang D;Guo Y;Wrighton SA;Cooke GE;Sadee W
通讯作者：
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影响因子：
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影响因子：
158.5
作者：
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影响因子：
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