Estudio de la implicación de polimorfismos genéticos del citocromo P450 y la glicoproteína-p en la terapéutica del trasplante renal

Abstract

There is great controversy regarding the clinical impact of genetic variants in patients receiving immunosuppressive calcineurin inhibitors (CNI). EETs play a protective role against the harmful processes in the kidney. In this work was evaluated retrospectively, the effect of polymorphisms in genes of enzymes involved in biodisposición of ICN (CYP3A4, CYP3A5 and ABCB1) and enzyme-producing genes EETs (CYP2C8 and CYP2J2) in the pharmacokinetics and/or pharmacodynamics of CNI in 171 renal transplant treated with Ciclosporina A (CsA; 68) and tacrolimus (103). Patients carrying the CYP3A5*1 functional allele had lower levels of tacrolimus and higher doses; enhanced effect if also carried the variant CYP3A4*1B. In patients treated with CsA, we have an association between the incidence of nephrotoxicity and the appearance of gingival hyperplasia in the presence of 4 or more allelic variants in the ABCB1 gene. You carry the CYP2C8*3 allele and receive a graft from a major donor of 48 years was associated with an increased risk of delayed renal function and creatinine clearance worse. Our results indicate that several variants in genes involved in the bioavailability of ICN or EETs can have an impact both on the pharmacokinetics of these immunosuppressants as in the transplant patient's clinical response. Therefore, their presence known a priori, in combination with other clinical and demographic data, can help improve the individualization of immunosuppressive therapy.