Impact of CYP3A7, CYP2D6 and ABCC2/ABCC3 polymorphisms on tacrolimus steady state concentrations in Bulgarian kidney transplant recipients

Polymorphisms in the genes of drug-metabolizing enzymes have potential to contribute inter-individual differences drug pharmacokinetics and toxicity. A custom next-generation sequencing (NGS) panel was used 71 kidney transplanted patients study polymorphisms 11 relevant metabolism immunosuppressive drugs. Cyclosporine tacrolimus concentrations were determined by a validated liquid chromatography with tandem mass spectrometry (LC-MS/MS) method. More than 1000 found studied genes, 45% them different non-synonymous variants. Eleven missense mutations observed CYP3A7 gene, resulting increased at day 21 post-transplantation (6.7 µg/L vs. 10.3 µg/L; p = 0.048). Two alleles encoding cytochrome P450 2D6 enzyme impaired function—CYP2D6*4 (non-functional) CYP2D6*10 (decreased function), group both associated higher levels 14 (10.1 0.021 9.7 0.036, 7.7 respectively). Altered function ABC transporters C3 C2 also TAC concentration. ABCC3 significantly influenced itself, but affecting ABCC2 resulted changes: 13.6 7.9 µg/L, (p 0.003) 20 versus 9.3 0.019). All associations checked for variants activity CYP3A4 CYP3A5. Despite its small size, points out that pharmacogenetics calcineurin inhibitors may be other besides