Influence of CYP3A and ABCB1 polymorphisms on cyclosporine concentrations in renal transplant recipients

Author:

Sun Bo1,Guo Yankun1,Gao Junwei1,Shi Weifeng1,Fan Guorong1,Li Xiaoyu1,Qiu Jianxin2,Qin Yan2,Liu Gaolin1

Affiliation:

1. Department of Pharmacy, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, P.R. China

2. Department of Renal Transplantation & Urology, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, P.R. China

Abstract

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.

Publisher

Future Medicine Ltd

Subject

Pharmacology,Genetics,Molecular Medicine

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