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Int. J. Mol. Sci. 2015, 16(9), 20168-20182; doi:10.3390/ijms160920168

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

1
Unidad de Farmacogenética, Instituto de Investigación Sanitaria La Fe, Hospital Universitario y Politécnico La Fe, Av. Fernando Abril Martorell 106, 46010 Valencia, Spain
2
Servicio de Farmacia, Hospital Universitario y Politécnico La Fe, Av. Fernando Abril Martorell 106, 46010 Valencia, Spain
3
Departamento Farmacología, Facultad de Medicina, Universidad de Valencia, Av. Blasco Ibáñez 15, 46010 Valencia, Spain
4
Unidad de Bioestadística, Instituto Investigación Sanitaria La Fe. Av. Fernando Abril Martorell 106, 46010 Valencia, Spain
5
Unidad de Trasplante Pulmonar, Hospital Universitario y Politécnico La Fe, Av. Fernando Abril Martorell 106, 46010 Valencia, Spain
6
Unidad de Farmacología Clínica, Área Clínica del Medicamento, Hospital Universitario y Politécnico La Fe, Av. Fernando Abril Martorell 106, 46010 Valencia, Spain
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Academic Editor: Sabrina Angelini
Received: 29 May 2015 / Revised: 13 July 2015 / Accepted: 13 August 2015 / Published: 25 August 2015
(This article belongs to the Special Issue Pharmacogenetics and Personalized Medicine)
View Full-Text   |   Download PDF [1147 KB, uploaded 27 August 2015]   |  

Abstract

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 (C0/Dc). 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. View Full-Text
Keywords: pharmacogenetics; lung transplantation; tacrolimus; mycophenolic acid; P-glycoprotein pharmacogenetics; lung transplantation; tacrolimus; mycophenolic acid; P-glycoprotein
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Ruiz, J.; Herrero, M.J.; Bosó, V.; Megías, J.E.; Hervás, D.; Poveda, J.L.; Escrivá, J.; Pastor, A.; Solé, A.; Aliño, S.F. Impact of Single Nucleotide Polymorphisms (SNPs) on Immunosuppressive Therapy in Lung Transplantation. Int. J. Mol. Sci. 2015, 16, 20168-20182.

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