title: Impact of Single Nucleotide Polymorphisms (SNPs) on Immunosuppressive Therapy in Lung Transplantation.
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.
authors: Unidad de Farmacogenética, Instituto de Investigación Sanitaria La Fe, Hospital Universitario y Politécnico La Fe, Av. Fernando Abril Martorell 106, 46010 Valencia, Spain. poveda_josand@gva.es.|Servicio de Farmacia, Hospital Universitario y Politécnico La Fe, Av. Fernando Abril Martorell 106, 46010 Valencia, Spain. poveda_josand@gva.es.
authors: Jesus
authors: J
authors: Ruiz
authors: Unidad de Farmacogenética, Instituto de Investigación Sanitaria La Fe, Hospital Universitario y Politécnico La Fe, Av. Fernando Abril Martorell 106, 46010 Valencia, Spain. maria.jose.herrero@uv.es.|Departamento Farmacología, Facultad de Medicina, Universidad de Valencia, Av. Blasco Ibáñez 15, 46010 Valencia, Spain. maria.jose.herrero@uv.es.
authors: María José
authors: MJ
authors: Herrero
authors: Unidad de Farmacogenética, Instituto de Investigación Sanitaria La Fe, Hospital Universitario y Politécnico La Fe, Av. Fernando Abril Martorell 106, 46010 Valencia, Spain. poveda_josand@gva.es.|Servicio de Farmacia, Hospital Universitario y Politécnico La Fe, Av. Fernando Abril Martorell 106, 46010 Valencia, Spain. poveda_josand@gva.es.
authors: Virginia
authors: V
authors: Bosó
authors: Unidad de Farmacogenética, Instituto de Investigación Sanitaria La Fe, Hospital Universitario y Politécnico La Fe, Av. Fernando Abril Martorell 106, 46010 Valencia, Spain. poveda_josand@gva.es.|Servicio de Farmacia, Hospital Universitario y Politécnico La Fe, Av. Fernando Abril Martorell 106, 46010 Valencia, Spain. poveda_josand@gva.es.
authors: Juan Eduardo
authors: JE
authors: Megías
authors: Unidad de Bioestadística, Instituto Investigación Sanitaria La Fe. Av. Fernando Abril Martorell 106, 46010 Valencia, Spain. bioestadistica@iislafe.es.
authors: David
authors: D
authors: Hervás
authors: Servicio de Farmacia, Hospital Universitario y Politécnico La Fe, Av. Fernando Abril Martorell 106, 46010 Valencia, Spain. poveda_josand@gva.es.
authors: Jose Luis
authors: JL
authors: Poveda
authors: Unidad de Trasplante Pulmonar, Hospital Universitario y Politécnico La Fe, Av. Fernando Abril Martorell 106, 46010 Valencia, Spain. escriva_juan@gva.es.
authors: Juan
authors: J
authors: Escrivá
authors: Unidad de Trasplante Pulmonar, Hospital Universitario y Politécnico La Fe, Av. Fernando Abril Martorell 106, 46010 Valencia, Spain. pastor_ampcol@gva.es.
authors: Amparo
authors: A
authors: Pastor
authors: Unidad de Trasplante Pulmonar, Hospital Universitario y Politécnico La Fe, Av. Fernando Abril Martorell 106, 46010 Valencia, Spain. sole_amp@gva.es.
authors: Amparo
authors: A
authors: Solé
authors: Unidad de Farmacogenética, Instituto de Investigación Sanitaria La Fe, Hospital Universitario y Politécnico La Fe, Av. Fernando Abril Martorell 106, 46010 Valencia, Spain. salvador.f.alino@uv.es.|Departamento Farmacología, Facultad de Medicina, Universidad de Valencia, Av. Blasco Ibáñez 15, 46010 Valencia, Spain. salvador.f.alino@uv.es.|Unidad de Farmacología Clínica, Área Clínica del Medicamento, Hospital Universitario y Politécnico La Fe, Av. Fernando Abril Martorell 106, 46010 Valencia, Spain. salvador.f.alino@uv.es.
authors: Salvador Francisco
authors: SF
authors: Aliño
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics; D000328:Adult; D051544:Cytochrome P-450 CYP3A / Q000235:genetics; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016040:Lung Transplantation / Q000009:adverse effects; D008875:Middle Aged; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics; D009173:Mycophenolic Acid / Q000493:pharmacokinetics; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide; D016559:Tacrolimus / Q000493:pharmacokinetics
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D051544:Cytochrome P-450 CYP3A; D007166:Immunosuppressive Agents; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009173:Mycophenolic Acid; D016559:Tacrolimus; C513055:ABCB1 protein, human; C000715087:ABCC2 protein, human
keywords: P-glycoprotein; lung transplantation; mycophenolic acid; pharmacogenetics; tacrolimus