engleski

PHARMACOGENOMICS OF IMMUNOSUPPRESSIVE DRUGS

Introduction: Standard immunosuppressive therapy in kidney transplantation is combination of mycophenolic acid, cyclosporine, tacrolimus, sirolimus or everolimus and corticosteroids that function on multiple pathways of the immune response. Immunosuppressants have narrow therapeutic window and exhibits an interindividual pharmacokinetic variability that affects the dose required to reach target concentration in blood. Genetic variability in some of the genes that affect absorption, distribution, metabolism and elimination (“pharmacogenes”) can significantly influence an individual’s response to the immunosuppressants and consequently the effectiveness of treatment and possible adverse drug events. The aim of the present study was to investigate the frequency of potentially actionable pharmacogenetics findings in the Croatian renal transplant recipients. Materials and methods: Study included 158 post renal transplantation patients treated with immunosuppressants. Genotyping of ABCB1 (3435C>T), ABCC2 (-24C>T), ABCG2 (421C>A), SLCO1B1 (521T>C), CYP3A4*22, CYP3A5*1 and UGT1A9 (-2152C>T) was performed by TaqMan real time PCR for discovery of clinically actionable variants. Results: At least one clinically actionable variant was found in 68 of 150 patients (45%). The frequencies of variant/minor alleles in the observed group were: ABCB1 (45%), ABCC2 (28%), SLCO1B1 (27%), ABCG2 (12%), CYP3A5 (12%), UGT1A9 (3%), CYP3A4 (1%). Conclusion: In the present study, we estimated the burden of pharmacogenetic variants in kidney transplant recipients that deserve different personalized treatment approach for optimized treatment. Implementation of pharmacogenetic testing to guide drug prescribing has potential to improve response and prevent adverse events.

immunosuppressive therapy ; kidney transplantation ; pharmacogenetics

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