CYP3A和ABCB1基因多态性对肾移植受者环孢素浓度的影响。
Influence of CYP3A and ABCB1 polymorphisms on cyclosporine concentrations in renal transplant recipients.
作者信息
Sun Bo, Guo Yankun, Gao Junwei, Shi Weifeng, Fan Guorong, Li Xiaoyu, Qiu Jianxin, Qin Yan, Liu Gaolin
机构信息
Department of Pharmacy, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, P.R. China.
Department of Renal Transplantation & Urology, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, P.R. China.
出版信息
Pharmacogenomics. 2017 Nov;18(16):1503-1513. doi: 10.2217/pgs-2017-0127. Epub 2017 Sep 27.
AIM
Cyclosporine is a substrate of CYP3A and ABCB1. This study examined the role of CYP3A and ABCB1 polymorphisms on cyclosporine pharmacokinetics in renal transplant recipients.
PATIENTS & METHODS: CYP3A and ABCB1 SNPs were detected in 521 recipients. The relationships of dose-adjusted concentrations with corresponding genotypes were investigated at the different terms.
RESULTS
CYP3A5 rs776746 and CYP3A7 rs10211 genotype affect C0/D at the short-term, medium-term and long-term after transplantation (p < 0.05). CYP3A7 rs2257401 genotype affects C2/D at the medium-term (p < 0.05). CYP3A4 rs4646437, CYP3A5 rs776746 and CYP3A7 rs2257401 genotype affect C2/D at the long-term (p < 0.05). There are no relationships between ABCB1 polymorphism and cyclosporine C/D.
CONCLUSION
CYP3A genetic factors (rs776746, rs4646437, rs2257401 and rs10211) were varied in different stages after transplantation. The role of CYP3A7 in cyclosporine metabolism requires further study.
目的
环孢素是细胞色素P450 3A（CYP3A）和ATP结合盒转运蛋白B1（ABCB1）的底物。本研究探讨CYP3A和ABCB1基因多态性对肾移植受者环孢素药代动力学的影响。
患者与方法
检测521例受者的CYP3A和ABCB1单核苷酸多态性（SNP）。研究不同时期剂量调整浓度与相应基因型的关系。
结果
CYP3A5基因rs776746位点和CYP3A7基因rs10211位点的基因型在移植后的短期、中期和长期均影响C0/D（p<0.05）。CYP3A7基因rs2257401位点的基因型在中期影响C2/D（p<0.05）。CYP3A4基因rs4646437位点、CYP3A5基因rs776746位点和CYP3A7基因rs2257401位点的基因型在长期影响C2/D（p<0.05）。ABCB1基因多态性与环孢素C/D之间无相关性。
结论
CYP3A基因因素（rs776746、rs4646437、rs2257401和rs10211）在移植后的不同阶段存在差异。CYP3A7在环孢素代谢中的作用有待进一步研究。
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