CYP3A4、CYP3A5、MDR1和NR1I2基因多态性对肾移植术后早期受者他克莫司谷浓度的交互作用。
Interactive effects of CYP3A4, CYP3A5, MDR1 and NR1I2 polymorphisms on tracrolimus trough concentrations in early postrenal transplant recipients.
作者信息
Li Jia-li, Liu Shu, Fu Qian, Zhang Yu, Wang Xue-ding, Liu Xiao-man, Liu Long-shan, Wang Chang-xi, Huang Min
机构信息
Institute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-sen University, 132 Waihuan Dong Road, University City, Guangzhou 510006, China.
Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng Dong Road, Guangzhou 510060, China.
出版信息
Pharmacogenomics. 2015;16(12):1355-65. doi: 10.2217/pgs.15.78. Epub 2015 Jul 31.
AIMS
To evaluate the influences of CYP3A4, CYP3A5, MDR1 and NR1I2 polymorphisms on tacrolimus concentration in early postrenal transplant recipients.
PATIENTS & METHODS: A total of 159 patients were included, dose-adjusted tacrolimus trough concentration on day 7 after transplantation (C0D7/D) was calculated and 10 SNPs in four genes were genotyped.
RESULTS
CYP3A53 explained 32.8% of variability of tacrolimus C0D7/D. CYP3A41G, MDR1 1236-2677-3435 diplotype and NR1I2 -25385C > T explained 21.4% of variability of tacrolimus C0D7/D in CYP3A5 nonexpressers.
CONCLUSION
CYP3A5*3 was the predominant determinant affecting tacrolimus concentration. Genotyping of CYP3A4/MDR1/NR1I2 polymorphisms may be helpful for better guiding tacrolimus dosing in CYP3A5 nonexpressers.
目的
评估CYP3A4、CYP3A5、MDR1和NR1I2基因多态性对肾移植术后早期受者他克莫司血药浓度的影响。
患者与方法
共纳入159例患者，计算移植后第7天剂量调整后的他克莫司谷浓度（C0D7/D），并对四个基因中的10个单核苷酸多态性（SNP）进行基因分型。
结果
CYP3A53解释了他克莫司C0D7/D变异性的32.8%。在CYP3A5非表达者中，CYP3A41G、MDR1 1236 - 2677 - 3435双倍型和NR1I2 - 25385C>T解释了他克莫司C0D7/D变异性的21.4%。
结论
CYP3A5*3是影响他克莫司血药浓度的主要决定因素。对CYP3A4/MDR1/NR1I2基因多态性进行基因分型可能有助于更好地指导CYP3A5非表达者的他克莫司给药。
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