Pharmacogenomics of mycophenolic acid in kidney transplantation: Contribution of immune response-related genes

Primer Autor
Hirata, Rosario Dominguez Crespo
Co-autores
Genvigir, Fabiana Dalla Vecchia
Hirata, Thiago Dominguez Crespo
Cerda, Alvaro
Hirata, Mario Hiroyuki
Título
Pharmacogenomics of mycophenolic acid in kidney transplantation: Contribution of immune response-related genes
Editorial
UNIV SAO PAULO, CONJUNTO QUIMICAS
Revista
BRAZILIAN JOURNAL OF PHARMACEUTICAL SCIENCES
Lenguaje
en
Resumen
Mycophenolic acid (MPA) inhibits IMPDH, involved in the guanosine nucleotides synthesis, and prevents DNA replication in immune cells. The repression of cell and humoral immunity by MPA induces allograft tolerance preventing acute rejection in solid organ transplantation. MPA is an effective and safe drug, but genetic and non-genetic factors have been implicated in the interindividual variability of drug response. Several studies have shown the impact of variants of pharmacokinetics or pharmacodynamics-related genes on MPA response in kidney transplantation. This review explored further the influence of genes involved in the immune response on clinical outcomes of kidney recipients on short-or long-term MPA treatment. Variants in genes related to T cell activation (CD28, CTL4, ICOS, PDPC1), pro-inflammatory cytokines (IL2, IL6, IL12A, IL12B, TNF, IFNG), immunomodulatory cytokines (IL4, IL10, TGFB1), and innate immune response (CD14, TLR2, TLR4) were shown to be associated with increased risk of acute rejection, graft function or survival, chronic graft nephropathy, viral infections or MPA-induced myelotoxicity. Some of the significant pharmacogenetic associations were confirmed by meta-analyses of kidney transplantation. These findings are suggestive that variants in immune response-related genes contribute to the variability of MPA response, and have potential application as biomarkers of acute rejection in kidney transplantation.
Fecha Publicación
2022
Tipo de Recurso
artículo original
doi
10.1590/s2175-97902022e201188
Formato Recurso
PDF
Palabras Claves
Immunosuppressive therapy
Mycophenolic acid
Kidney transplantation
Pharmacogenomics
Immune response
Ubicación del archivo
Categoría OCDE
Farmacología y farmacia
Materias
Terapia inmunosupresora
Ácido micofenólico
Trasplante de riñón
Farmacogenómica
Respuesta inmune
Identificador del recurso (Mandatado-único)
artículo original
Versión del recurso (Recomendado-único)
versión publicada
License
CC BY 4.0
Condición de la licencia (Recomendado-repetible)
CC BY 4.0
Derechos de acceso
acceso abierto
Access Rights
acceso abierto
Id de Web of Science
WOS:000919890100001
ISSN
1984-8250
Tipo de ruta
Verde# dorado
Categoría WOS
Farmacología y farmacia
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