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Impact of Single Nucleotide Polymorphisms (SNPs) on Immunosuppressive Therapy in Lung Transplantation

Lung transplant patients present important variability in immunosuppressant blood concentrations during the first months after transplantation. Pharmacogenetics could explain part of this interindividual variability. We evaluated SNPs in genes that have previously shown correlations in other kinds o...

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Autores principales: Ruiz, Jesus, Herrero, María José, Bosó, Virginia, Megías, Juan Eduardo, Hervás, David, Poveda, Jose Luis, Escrivá, Juan, Pastor, Amparo, Solé, Amparo, Aliño, Salvador Francisco
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4613195/
https://www.ncbi.nlm.nih.gov/pubmed/26307985
http://dx.doi.org/10.3390/ijms160920168
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author Ruiz, Jesus
Herrero, María José
Bosó, Virginia
Megías, Juan Eduardo
Hervás, David
Poveda, Jose Luis
Escrivá, Juan
Pastor, Amparo
Solé, Amparo
Aliño, Salvador Francisco
author_facet Ruiz, Jesus
Herrero, María José
Bosó, Virginia
Megías, Juan Eduardo
Hervás, David
Poveda, Jose Luis
Escrivá, Juan
Pastor, Amparo
Solé, Amparo
Aliño, Salvador Francisco
author_sort Ruiz, Jesus
collection PubMed
description Lung transplant patients present important variability in immunosuppressant blood concentrations during the first months after transplantation. Pharmacogenetics could explain part of this interindividual variability. We evaluated SNPs in genes that have previously shown correlations in other kinds of solid organ transplantation, namely ABCB1 and CYP3A5 genes with tacrolimus (Tac) and ABCC2, UGT1A9 and SLCO1B1 genes with mycophenolic acid (MPA), during the first six months after lung transplantation (51 patients). The genotype was correlated to the trough blood drug concentrations corrected for dose and body weight (C(0)/D(c)). The ABCB1 variant in rs1045642 was associated with significantly higher Tac concentration, at six months post-transplantation (CT vs. CC). In the MPA analysis, CT patients in ABCC2 rs3740066 presented significantly lower blood concentrations than CC or TT, three months after transplantation. Other tendencies, confirming previously expected results, were found associated with the rest of studied SNPs. An interesting trend was recorded for the incidence of acute rejection according to NOD2/CARD15 rs2066844 (CT: 27.9%; CC: 12.5%). Relevant SNPs related to Tac and MPA in other solid organ transplants also seem to be related to the efficacy and safety of treatment in the complex setting of lung transplantation.
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spelling pubmed-46131952015-10-26 Impact of Single Nucleotide Polymorphisms (SNPs) on Immunosuppressive Therapy in Lung Transplantation Ruiz, Jesus Herrero, María José Bosó, Virginia Megías, Juan Eduardo Hervás, David Poveda, Jose Luis Escrivá, Juan Pastor, Amparo Solé, Amparo Aliño, Salvador Francisco Int J Mol Sci Article Lung transplant patients present important variability in immunosuppressant blood concentrations during the first months after transplantation. Pharmacogenetics could explain part of this interindividual variability. We evaluated SNPs in genes that have previously shown correlations in other kinds of solid organ transplantation, namely ABCB1 and CYP3A5 genes with tacrolimus (Tac) and ABCC2, UGT1A9 and SLCO1B1 genes with mycophenolic acid (MPA), during the first six months after lung transplantation (51 patients). The genotype was correlated to the trough blood drug concentrations corrected for dose and body weight (C(0)/D(c)). The ABCB1 variant in rs1045642 was associated with significantly higher Tac concentration, at six months post-transplantation (CT vs. CC). In the MPA analysis, CT patients in ABCC2 rs3740066 presented significantly lower blood concentrations than CC or TT, three months after transplantation. Other tendencies, confirming previously expected results, were found associated with the rest of studied SNPs. An interesting trend was recorded for the incidence of acute rejection according to NOD2/CARD15 rs2066844 (CT: 27.9%; CC: 12.5%). Relevant SNPs related to Tac and MPA in other solid organ transplants also seem to be related to the efficacy and safety of treatment in the complex setting of lung transplantation. MDPI 2015-08-25 /pmc/articles/PMC4613195/ /pubmed/26307985 http://dx.doi.org/10.3390/ijms160920168 Text en © 2015 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Ruiz, Jesus
Herrero, María José
Bosó, Virginia
Megías, Juan Eduardo
Hervás, David
Poveda, Jose Luis
Escrivá, Juan
Pastor, Amparo
Solé, Amparo
Aliño, Salvador Francisco
Impact of Single Nucleotide Polymorphisms (SNPs) on Immunosuppressive Therapy in Lung Transplantation
title Impact of Single Nucleotide Polymorphisms (SNPs) on Immunosuppressive Therapy in Lung Transplantation
title_full Impact of Single Nucleotide Polymorphisms (SNPs) on Immunosuppressive Therapy in Lung Transplantation
title_fullStr Impact of Single Nucleotide Polymorphisms (SNPs) on Immunosuppressive Therapy in Lung Transplantation
title_full_unstemmed Impact of Single Nucleotide Polymorphisms (SNPs) on Immunosuppressive Therapy in Lung Transplantation
title_short Impact of Single Nucleotide Polymorphisms (SNPs) on Immunosuppressive Therapy in Lung Transplantation
title_sort impact of single nucleotide polymorphisms (snps) on immunosuppressive therapy in lung transplantation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4613195/
https://www.ncbi.nlm.nih.gov/pubmed/26307985
http://dx.doi.org/10.3390/ijms160920168
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