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Pharmacogenomics of mycophenolic acid in kidney transplantation: Contribution of immune response-related genes
Hirata, Rosario Dominguez Crespo; Genvigir, Fabiana Dalla Vecchia; Hirata, Thiago Dominguez Crespo; Cerda, Alvaro; Hirata, Mario Hiroyuki.
  • Hirata, Rosario Dominguez Crespo; University of Sao Paulo. School of Pharmaceutical Sciences. Department of Clinical & Toxicological Analyses. Sao Paulo. BR
  • Genvigir, Fabiana Dalla Vecchia; University of Sao Paulo. School of Pharmaceutical Sciences. Department of Clinical & Toxicological Analyses. Sao Paulo. BR
  • Hirata, Thiago Dominguez Crespo; University of Sao Paulo. School of Pharmaceutical Sciences. Department of Clinical & Toxicological Analyses. Sao Paulo. BR
  • Cerda, Alvaro; Universidad de La Frontera. Center of Excellence in Translational Medicine. Department of Basic Sciences. Temuco. CL
  • Hirata, Mario Hiroyuki; University of Sao Paulo. School of Pharmaceutical Sciences. Department of Clinical & Toxicological Analyses. Sao Paulo. BR
Braz. J. Pharm. Sci. (Online) ; 58: e201188, 2022. tab, graf
Artículo en Inglés | LILACS | ID: biblio-1420506
ABSTRACT
Abstract 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.
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Texto completo: Disponible Índice: LILACS (Américas) Asunto principal: Farmacogenética / Trasplante de Riñón / Ácido Micofenólico Idioma: Inglés Revista: Braz. J. Pharm. Sci. (Online) Asunto de la revista: Farmacologia / Terapˆutica / Toxicologia Año: 2022 Tipo del documento: Artículo País de afiliación: Brasil / Chile Institución/País de afiliación: Universidad de La Frontera/CL / University of Sao Paulo/BR

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Texto completo: Disponible Índice: LILACS (Américas) Asunto principal: Farmacogenética / Trasplante de Riñón / Ácido Micofenólico Idioma: Inglés Revista: Braz. J. Pharm. Sci. (Online) Asunto de la revista: Farmacologia / Terapˆutica / Toxicologia Año: 2022 Tipo del documento: Artículo País de afiliación: Brasil / Chile Institución/País de afiliación: Universidad de La Frontera/CL / University of Sao Paulo/BR