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

International Journal of Molecular Sciences

Jesus Ruiz¹  Mar໚ José Herrero¹  Virginia Bosó¹  Juan Eduardo Meg໚s¹  David Hervás²  Jose Luis Poveda⁴  Juan Escrivá³  Amparo Pastor³  Amparo Solé³  Salvador Francisco Aliño¹ 

[1] Unidad de Farmacogenética, Instituto de Investigación Sanitaria La Fe, Hospital Universitario y Politécnico La Fe, Av. Fernando Abril Martorell 106, 46010 Valencia, Spain; E-Mails:;Unidad de Bioestadística, Instituto Investigación Sanitaria La Fe. Av. Fernando Abril Martorell 106, 46010 Valencia, Spain; E-Mail:;Unidad de Trasplante Pulmonar, Hospital Universitario y Politécnico La Fe, Av. Fernando Abril Martorell 106, 46010 Valencia, Spain; E-Mails:;Servicio de Farmacia, Hospital Universitario y Politécnico La Fe, Av. Fernando Abril Martorell 106, 46010 Valencia, Spain; E-Mail:

关键词: pharmacogenetics;    lung transplantation;    tacrolimus;    mycophenolic acid;    P-glycoprotein;   

DOI  :  10.3390/ijms160920168

来源: mdpi

【 摘 要 】

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/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.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.