Pharmacogenomics of mycophenolic acid in kidney transplantation: Contribution of immune response-related genes
Autor(a) principal: | |
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Data de Publicação: | 2023 |
Outros Autores: | , , , |
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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oai:revistas.usp.br:article/207743 |
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Brazilian Journal of Pharmaceutical Sciences |
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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 |
_version_ |
1821325166311899136 |