title: The potential of steroids and xenobiotic receptor polymorphisms in forecasting cyclosporine pharmacokinetic variability in young kidney transplant recipients.
abstract: The steroids and xenobiotics receptor (SXR) up-regulates the expression and the synthesis of key enzymes in CyA metabolism. In this study, we examined the possible interactions between CyA exposure and SXR polymorphisms during the first year after renal transplantation. The study involved 66 pediatric renal transplant recipients (25 women and 41 men, mean age 13.9 ± 7.4 yr). All patients were genotyped for two sequence variations in the NR1I2 gene: g.-205_-200delGAGAAG and 7635 A>G. CyA trough levels and CyA weight-adjusted daily dose were recorded at 30, 90, 180, and 360 days after transplantation and compared between the different genotypes. A third newly discovered SXR polymorphism was characterized and also included in the study. CyA trough levels and CyA weight-adjusted daily dose were comparable on four time points throughout the first year post-transplant in all three groups. GEE showed a significant reduction in weight-adjusted CyA daily dose in patients carrying the deletion of 6 bp in SXR with a significant group-by-time effect that persisted also when analysis was corrected for age, prednisone dose, and acute rejection episodes. In our group of patients, only the g.-205_-200delGAGAAG SXR polymorphism was able to influence the metabolism of CyA continuously, during the first year after transplantation.
authors: Department of Clinical Sciences and Community Health, University of Milan Medical School, Milan, Italy. mariano.ferraresso@unimi.it
authors: Mariano
authors: M
authors: Ferraresso
authors: Stefano
authors: S
authors: Turolo
authors: Mirco
authors: M
authors: Belinghieri
authors: Amedea Silvia
authors: AS
authors: Tirelli
authors: Paolo
authors: P
authors: Grillo
authors: Elena
authors: E
authors: Groppali
authors: Alberto
authors: A
authors: Edefonti
authors: Luciana
authors: L
authors: Ghio
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D016572:Cyclosporine / Q000493:pharmacokinetics*; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016030:Kidney Transplantation / Q000379:methods*; D008297:Male; D010597:Pharmacogenetics / Q000379:methods*; D011110:Polymorphism, Genetic; D000077297:Pregnane X Receptor; D011987:Receptors, Steroid / Q000235:genetics*; D051437:Renal Insufficiency / Q000235:genetics* / Q000628:therapy; D013256:Steroids / Q000627:therapeutic use*; D013997:Time Factors; D015262:Xenobiotics / Q000627:therapeutic use*
chemical_list: D007166:Immunosuppressive Agents; C000625852:NR1I2 protein, human; D000077297:Pregnane X Receptor; D011987:Receptors, Steroid; D013256:Steroids; D015262:Xenobiotics; D016572:Cyclosporine