Abstract
BackgroundWe evaluated the role of CYP3A5, ABCB1 and SXR gene polymorphisms in the occurrence of acute kidney rejection in a cohort of pediatric renal transplant recipients.MethodsForty-nine patients were genotyped for CYP3A5, ABCB1 and SXR polymorphisms and evaluated with tacrolimus through levels in a retrospective monocenter study.ResultsPatients with the A allele of CYP3A5 treated with tacrolimus had a higher risk of acute rejection than those without the A allele, while patients carrying the homozygous GG variant for SXR A7635GG did not show any episode of acute rejection.ConclusionGenetic analysis of polymorphisms implicated in drug metabolism and tacrolimus trough levels may help to forecast the risk of acute rejection and individualize drug dosage in children undergoing renal transplantation.
Highlights
We evaluated the role of Cytochrome P-450 3A5 (CYP3A5), ABCB1 and Steroid xenobiotic receptor (SXR) gene polymorphisms in the occurrence of acute kidney rejection in a cohort of pediatric renal transplant recipients
It is well known that polymorphisms of the intracellular metabolizer enzyme CYP and the trans-membrane transport protein ABCB1 may influence enzymatic intracellular activity, modifying drugs metabolism [11,12,13,14,15,16,17,18,19]
Forty-nine pediatric patients who received a kidney transplant between January 2000 and December 2010, from either deceased (44) or living (5) donors, and who were treated with an immunosuppressive protocol including tacrolimus and with a complete set of tacrolimus trough blood levels and pharmacogenomic data were available for evaluation
Summary
We evaluated the role of CYP3A5, ABCB1 and SXR gene polymorphisms in the occurrence of acute kidney rejection in a cohort of pediatric renal transplant recipients. Methods: Forty-nine patients were genotyped for CYP3A5, ABCB1 and SXR polymorphisms and evaluated with tacrolimus through levels in a retrospective monocenter study. Results: Patients with the A allele of CYP3A5 treated with tacrolimus had a higher risk of acute rejection than those without the A allele, while patients carrying the homozygous GG variant for SXR A7635GG did not show any episode of acute rejection. Tacrolimus is the main calcineurin inhibitor used in kidney transplantation in high-income countries [10]. It is metabolized by cytochrome P-450, encoded by the CYP genes cluster. ABCB1 polymorphisms may affect, either positively or negatively, tacrolimus metabolism [21], even if to a lesser
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