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RESEARCH PRODUCT
Impact of Single Nucleotide Polymorphisms (SNPs) on Immunosuppressive Therapy in Lung Transplantation.
Virginia BosóDavid HervásJosé Luis PovedaJuan Eduardo MegíasAmparo SoléAmparo PastorJesus RuizSalvador F. AliñoSalvador F. AliñoMaría José HerreroMaría José HerreroJuan Escrivásubject
Adultmedicine.medical_specialtyATP Binding Cassette Transporter Subfamily Bmedicine.medical_treatment<i>P</i>-glycoproteinSingle-nucleotide polymorphismPharmacologyP-glycoproteinGastroenterologyPolymorphism Single NucleotideCatalysisMycophenolic acidTacrolimusArticlelcsh:ChemistryInorganic ChemistryInternal medicineBlood drugmedicinelung transplantationLung transplantationCytochrome P-450 CYP3AHumansPhysical and Theoretical Chemistrylcsh:QH301-705.5Molecular BiologySpectroscopybiologyOrganic ChemistryGeneral MedicineMiddle AgedMycophenolic AcidTacrolimusMultidrug Resistance-Associated Protein 2Computer Science ApplicationsTransplantationlcsh:Biology (General)lcsh:QD1-999Pharmacogeneticsbiology.proteinMultidrug Resistance-Associated ProteinsSLCO1B1PharmacogeneticsImmunosuppressive Agentsmedicine.drugdescription
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%
year | journal | country | edition | language |
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2015-08-25 | International journal of molecular sciences |