A new donors' CYP3A5 and recipients' CYP3A4 cluster predicting tacrolimus disposition, and new-onset hypertension in Chinese liver transplant patients.
A new donors' CYP3A5 and recipients' CYP3A4 cluster predicting tacrolimus disposition, and new-onset hypertension in Chinese liver transplant patients.
复制标题
新供者 CYP3A5 和受者 CYP3A4 簇预测中国肝移植患者的他克莫司处置和新发高血压
DOI：
10.18632/oncotarget.19606
复制
发表时间：
2017-09-19
期刊：
影响因子：
--
通讯作者：
Fan J
中科院分区：
文献类型：
--
作者：
Liu Y;Zhang T;Zhang X;Ye L;Gu H;Zhong L;Sun H;Song C;Peng Z;Fan J
本研究的目的是探讨他克莫司（Tac）的个体化治疗，以及肝移植（LT）后的并发症与已知的遗传因素和临床因素。在这项回顾性研究中，纳入了2007年7月至2015年3月中国肝移植登记中心（CLTR）数据库中的两个队列（n=170）。供者CYP 3A 5 *3和受者CYP 3A 4 *1G与4周时Tac药代动力学均相关（均P<0.05），但受者CYP 3A 4 *1G在2周时与Tac药代动力学几乎相关（P=0.055）。供体CYP 3A 5 *3、受体CYP 3A 4 *1G和总胆红素（TBL）模型预测Tac处置仅在第1、2和3周优于供体CYP 3A 5 *3（分别为P=0.010、P=0.007和P=0.010），但在第4周不明显（P=0.297）。此外，根据上述模型，当考虑假阳性率R= 10%后P值大于或等于0.6685时，认为患者具有更快的代谢。有趣的是，我们发现，如果供体CYP 3A 5 *3和受体CYP 3A 4 *1G基因型的组合中存在大于或等于两个等位基因A，则在第1、2和3周时Tac C/D比率较低除第4周（P=0.082）外，其他各组间差异均有统计学意义（P<0.001，P=0.001，P<0.001），且新发高血压的概率较低（P<0.001）。这些数据提供了一个综合的方法来预测个体患者的Tac剂量需求的潜在基础，并提供了一个策略，有效地预防，早期诊断新发高血压在中国的LT接受者。
The purpose of the current study was to investigate individualized therapy of tacrolimus (Tac), as well as complications after liver transplantation (LT) with the known genetic determinants and clinical factors. In this retrospective study, two cohorts (n=170) from the China Liver Transplant Registry (CLTR) database from July 2007 to March 2015 were included. Both donors’ CYP3A5*3 and recipients’ CYP3A4*1G had a correlation with Tac pharmacokinetics at four weeks (all P<0.05), except recipients’ CYP3A4*1G nearly had an association at week 2 (P=0.055). The model of donors’ CYP3A5*3, recipients’ CYP3A4*1G, and total bilirubin (TBL), for the prediction of Tac disposition, was better than donors’ CYP3A5*3 only at week 1, 2, and 3 (P=0.010, P=0.007, and P=0.010, respectively), but not apparent at week 4 (P=0.297). Besides, when the P value was greater than or equal to 0.6685 after considering the false-positive rate R=10%, the patients were considered to have a faster metabolism, according to the mentioned model. Interestingly, we found that if more than or equal to two alleles A were present in the combination of donors’ CYP3A5*3 and recipients’ CYP3A4*1G genotype, there was a lower Tac C/D ration at week 1, 2, and 3 (P<0.001, P=0.001, and P<0.001), except at week 4 (P=0.082), and the probability of new-onset hypertension was lesser (P<0.001). These data provided a potential basis for a comprehensive approach to predicting the Tac dose requirement in individual patients and provided a strategy for the effective prevention, early diagnosis of new-onset hypertension in Chinese LT recipients.
登录
查看更多内容
影响因子：
6.2
作者：
Jacobson PA;Oetting WS;Brearley AM;Leduc R;Guan W;Schladt D;Matas AJ;Lamba V;Julian BA;Mannon RB;Israni A;DeKAF Investigators
通讯作者：
DeKAF Investigators
DOI：
10.1016/j.healun.2011.08.001
发表时间：
2011-12
期刊：
The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation
影响因子：
--
作者：
Gijsen V;Mital S;van Schaik RH;Soldin OP;Soldin SJ;van der Heiden IP;Nulman I;Koren G;de Wildt SN
通讯作者：
de Wildt SN
影响因子：
2.1
作者：
Du, Jing;Xing, Qinghe;He, Lin
通讯作者：
He, Lin
影响因子：
--
作者：
Pan GH;Chen Z;Xu L;Zhu JH;Xiang P;Ma JJ;Peng YW;Li GH;Chen XY;Fang JL;Guo YH;Zhang L;Liu LS
通讯作者：
Liu LS
影响因子：
4.7
作者：
McCarty, Mark F.
通讯作者：
McCarty, Mark F.