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

Detalhes bibliográficos
Autor(a) principal: Hirata, Rosario Dominguez Crespo
Data de Publicação: 2023
Outros Autores: Genvigir, Fabiana Dalla Vecchia, Hirata, Thiago Dominguez Crespo, Cerda, Alvaro, Hirata, Mario Hiroyuki
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Brazilian Journal of Pharmaceutical Sciences
Texto Completo: https://www.revistas.usp.br/bjps/article/view/207743
Resumo: 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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spelling Pharmacogenomics of mycophenolic acid in kidney transplantation: Contribution of immune response-related genesImmunosuppressive therapyMycophenolic acidKidney transplantation PharmacogenomicsImmune responseMycophenolic 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.Universidade de São Paulo. Faculdade de Ciências Farmacêuticas2023-02-06info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://www.revistas.usp.br/bjps/article/view/20774310.1590/s2175-97902022e201188Brazilian Journal of Pharmaceutical Sciences; Vol. 58 (2022)Brazilian Journal of Pharmaceutical Sciences; v. 58 (2022)Brazilian Journal of Pharmaceutical Sciences; Vol. 58 (2022)2175-97901984-8250reponame:Brazilian Journal of Pharmaceutical Sciencesinstname:Universidade de São Paulo (USP)instacron:USPenghttps://www.revistas.usp.br/bjps/article/view/207743/197331Copyright (c) 2022 Brazilian Journal of Pharmaceutical Scienceshttps://creativecommons.org/licenses/by/4.0info:eu-repo/semantics/openAccess Hirata, Rosario Dominguez CrespoGenvigir, Fabiana Dalla VecchiaHirata, Thiago Dominguez CrespoCerda, AlvaroHirata, Mario Hiroyuki 2023-08-18T20:06:49Zoai:revistas.usp.br:article/207743Revistahttps://www.revistas.usp.br/bjps/indexPUBhttps://old.scielo.br/oai/scielo-oai.phpbjps@usp.br||elizabeth.igne@gmail.com2175-97901984-8250opendoar:2023-08-18T20:06:49Brazilian Journal of Pharmaceutical Sciences - Universidade de São Paulo (USP)false
dc.title.none.fl_str_mv Pharmacogenomics of mycophenolic acid in kidney transplantation: Contribution of immune response-related genes
title Pharmacogenomics of mycophenolic acid in kidney transplantation: Contribution of immune response-related genes
spellingShingle Pharmacogenomics of mycophenolic acid in kidney transplantation: Contribution of immune response-related genes
Hirata, Rosario Dominguez Crespo
Immunosuppressive therapy
Mycophenolic acid
Kidney transplantation
Pharmacogenomics
Immune response
title_short Pharmacogenomics of mycophenolic acid in kidney transplantation: Contribution of immune response-related genes
title_full Pharmacogenomics of mycophenolic acid in kidney transplantation: Contribution of immune response-related genes
title_fullStr Pharmacogenomics of mycophenolic acid in kidney transplantation: Contribution of immune response-related genes
title_full_unstemmed Pharmacogenomics of mycophenolic acid in kidney transplantation: Contribution of immune response-related genes
title_sort Pharmacogenomics of mycophenolic acid in kidney transplantation: Contribution of immune response-related genes
author Hirata, Rosario Dominguez Crespo
author_facet Hirata, Rosario Dominguez Crespo
Genvigir, Fabiana Dalla Vecchia
Hirata, Thiago Dominguez Crespo
Cerda, Alvaro
Hirata, Mario Hiroyuki
author_role author
author2 Genvigir, Fabiana Dalla Vecchia
Hirata, Thiago Dominguez Crespo
Cerda, Alvaro
Hirata, Mario Hiroyuki
author2_role author
author
author
author
dc.contributor.author.fl_str_mv Hirata, Rosario Dominguez Crespo
Genvigir, Fabiana Dalla Vecchia
Hirata, Thiago Dominguez Crespo
Cerda, Alvaro
Hirata, Mario Hiroyuki
dc.subject.por.fl_str_mv Immunosuppressive therapy
Mycophenolic acid
Kidney transplantation
Pharmacogenomics
Immune response
topic Immunosuppressive therapy
Mycophenolic acid
Kidney transplantation
Pharmacogenomics
Immune response
description 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.
publishDate 2023
dc.date.none.fl_str_mv 2023-02-06
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv https://www.revistas.usp.br/bjps/article/view/207743
10.1590/s2175-97902022e201188
url https://www.revistas.usp.br/bjps/article/view/207743
identifier_str_mv 10.1590/s2175-97902022e201188
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv https://www.revistas.usp.br/bjps/article/view/207743/197331
dc.rights.driver.fl_str_mv Copyright (c) 2022 Brazilian Journal of Pharmaceutical Sciences
https://creativecommons.org/licenses/by/4.0
info:eu-repo/semantics/openAccess
rights_invalid_str_mv Copyright (c) 2022 Brazilian Journal of Pharmaceutical Sciences
https://creativecommons.org/licenses/by/4.0
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Universidade de São Paulo. Faculdade de Ciências Farmacêuticas
publisher.none.fl_str_mv Universidade de São Paulo. Faculdade de Ciências Farmacêuticas
dc.source.none.fl_str_mv Brazilian Journal of Pharmaceutical Sciences; Vol. 58 (2022)
Brazilian Journal of Pharmaceutical Sciences; v. 58 (2022)
Brazilian Journal of Pharmaceutical Sciences; Vol. 58 (2022)
2175-9790
1984-8250
reponame:Brazilian Journal of Pharmaceutical Sciences
instname:Universidade de São Paulo (USP)
instacron:USP
instname_str Universidade de São Paulo (USP)
instacron_str USP
institution USP
reponame_str Brazilian Journal of Pharmaceutical Sciences
collection Brazilian Journal of Pharmaceutical Sciences
repository.name.fl_str_mv Brazilian Journal of Pharmaceutical Sciences - Universidade de São Paulo (USP)
repository.mail.fl_str_mv bjps@usp.br||elizabeth.igne@gmail.com
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