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

Pharmacogenomics. 2017 Nov;18(16):1503-1513. doi: 10.2217/pgs-2017-0127. Epub 2017 Sep 27.

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.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B / genetics
  • Adult
  • Cyclosporine / pharmacokinetics*
  • Cytochrome P-450 CYP3A / genetics*
  • Female
  • Genotype
  • Humans
  • Kidney / metabolism
  • Kidney Transplantation / methods
  • Male
  • Polymorphism, Single Nucleotide / genetics*
  • Transplant Recipients

Substances

  • ABCB1 protein, human
  • ATP Binding Cassette Transporter, Subfamily B
  • Cyclosporine
  • Cytochrome P-450 CYP3A