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

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.

Keywords: ABCB1; CYP3A; cyclosporine; dose-adjusted concentration; gene polymorphisms; individualized therapy; renal transplant recipient.