Long-term effects of ABCB1 and SXR SNPs on the systemic exposure to cyclosporine in pediatric kidney transplant patients

Mariano Ferraresso, Mirco Belingheri, Stefano Turolo, Luciana Ghio, Amedea Silvia Tirelli, Paolo Grillo, Marta Lepore, Alberto Edefonti

Research output: Contribution to journalArticlepeer-review

Abstract

Aim: Cyclosporine is characterized by a wide interindividual variability in its pharmacokinetics. The objective of this study was to evaluate the effects of ABCB1 and SXR SNPs on cyclosporine exposure in a group of kidney transplant patients followed up from childhood to adulthood. Patients & methods: Recipients were genotyped for ABCB1 C1236T, G2677T/A and C3435T, and for SXR RS3842689 and A7635G. Dose-adjusted trough levels and weight-adjusted daily doses were compared among patients according to allelic status by a generalized estimation equation approach that allows longitudinal data analyses. Results: A genotype-dependent effect was found in all ABCB1 genotypes and in one of the SXR SNPs. This effect was particularly evident for the TT genotype of the ABCB1 G2677T/A SNP, the TT genotype of the ABCB1 C3435T SNP and for heterozygotes of the deletion of 6 bp in the promoter region of SXR. Conclusion: The presence of specific ABCB1 and SXR SNPs could significantly affect cyclosporine exposure during a kidney transplant patients development from childhood to adulthood in a time-dependent fashion. Original submitted 3 May 2013; Revision submitted 25 July 201.

Original languageEnglish
Pages (from-to)1605-1613
Number of pages9
JournalPharmacogenomics
Volume14
Issue number13
DOIs
Publication statusPublished - Oct 2013

Keywords

  • ABCB1
  • cyclosporine
  • developmental pharmacology
  • pediatric kidney transplantation
  • pharmacogenetic
  • pharmacokinetic
  • single nucleotide polymorphism
  • SXR

ASJC Scopus subject areas

  • Pharmacology
  • Genetics
  • Molecular Medicine

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