| Journal: | Brazilian Journal of Pharmaceutical Sciences |
| Database: | PERIÓDICA |
| System number: | 000452205 |
| ISSN: | 1984-8250 |
| Authors: | Hirata, Rosario Dominguez Crespo1 Genvigir, Fabiana Dalla Vecchia1 Hirata, Thiago Dominguez Crespo1 Cerda, Alvaro2 Hirata, Mario Hiroyuki1 |
| Institutions: | 1Universidade de Sao Paulo, Faculdade de Ciencias Farmaceuticas, Sao Paulo. Brasil 2Universidad de La Frontera, Centro de Excelencia en Medicina Traslacional, Temuco, Cautín. Chile |
| Year: | 2022 |
| Volumen: | 58 |
| Country: | Brasil |
| Language: | Inglés |
| Document type: | Artículo |
| Approach: | Experimental, aplicado |
| English 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 |
| Disciplines: | Química, Medicina |
| Keyword: | Nefrología, Inmunología, Farmacología, Terapia inmunosupresora, Ácido micofenólico, Trasplante renal, Farmacogenómica, Respuesta inmune |
| Keyword: | Nephrology, Immunology, Pharmacology, Immunosuppressive therapy, Mycophenolic acid, Kidney transplantation, Pharmacogenomics, Immune response |
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